Search

Background: In 2006, the National Institute of Clinical and Health Excellence (NICE) guidelines for Obsessive Compulsive Disorder (OCD) recommended anti-psychotics as a class for SSRI treatment resistant OCD. The article aims to systematically review and conduct a meta-analysis on the clinical effectiveness of atypical anti-psychotics augmenting an SSRI., Methods: Studies that were double-blind randomized controlled trials of an atypical antipsychotic against a placebo, for a minimum of 4 weeks, in adults with OCD, were included. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores were the primary outcome measure. Inclusion criteria included Y-BOCS score of 16 or more and at least one adequate trial of a SSRI or clomipramine for at least 8 weeks prior to randomization. Data sources included Medline, Embase, PsycINFO, Cochrane Database of Systematic Reviews (CDSR), trial registries and pharmaceutical databases and manufacturers up to September 2013. Forest-plots were drawn to display differences between drug and placebo on the Y-BOCS., Results: Two studies found aripiprazole to be effective in the short-term. There was a small effect-size for risperidone or anti-psychotics in general in the short-term. We found no evidence for the effectiveness of quetiapine or olanzapine in comparison to placebo., Conclusions: Risperidone and aripiprazole can be used cautiously at a low dose as an augmentation agent in non-responders to SSRIs and CBT but should be monitored at 4 weeks to determine efficacy.

Few randomized controlled trials (RCTs) exist examining the efficacy of behavior therapy (BT) or serotonin reuptake inhibitors (SRIs) for the treatment of trichotillomania (TTM), with no examination of treatment moderators. The present meta-analysis synthesized the treatment effect sizes (ES) of BT and SRI relative to comparison conditions, and examined moderators of treatment. A comprehensive literature search identified 11 RCTs that met inclusion criteria. Clinical characteristics (e.g., age, comorbidity, therapeutic contact hours), outcome measures, treatment subtypes (e.g., SRI subtype, BT subtype), and ES data were extracted. The standardized mean difference of change in hair pulling severity was the outcome measure. A random effects meta-analysis found a large pooled ES for BT (ES = 1.41, p < 0.001). BT trials with greater therapeutic contact hours exhibited larger ES (p = 0.009). Additionally, BT trials that used mood enhanced therapeutic techniques exhibited greater ES relative to trials including only traditional BT components (p = 0.004). For SRI trials, a random effects meta-analysis identified a moderate pooled ES (ES = 0.41, p = 0.02). Although clomipramine exhibited larger ES relative to selective serotonin reuptake inhibitors, the difference was not statistically significant. Publication bias was not identified for either treatment. BT yields large treatment effects for TTM, with further examination needed to disentangle confounded treatment moderators. SRI trials exhibited a moderate pooled ES, with no treatment moderators identified. Sensitivity analyses highlighted the need for further RCTs of SRIs, especially among youth with TTM., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Antidepressants are widely used to treat chronic neuropathic pain (pain due to nerve damage), usually in doses below those at which they exert antidepressant effects. An earlier review that included all antidepressants for neuropathic pain is being replaced by new reviews of individual drugs examining individual neuropathic pain conditions.Desipramine is a tricyclic antidepressant that is occasionally used for treating neuropathic pain., Objectives: To assess the analgesic efficacy of desipramine for chronic neuropathic pain in adults, and to assess the associated adverse events., Search Methods: We searched CENTRAL, MEDLINE, and EMBASE from inception to 29 April 2014, and the reference lists of retrieved papers and other reviews. We also used our own hand searched database to identify older studies, and two clinical trials databases for ongoing or unpublished studies., Selection Criteria: We included randomised, double-blind studies of at least two weeks duration comparing desipramine with placebo or another active treatment in chronic neuropathic pain. Participants were adults aged 18 years and over. We included only full journal publication articles., Data Collection and Analysis: Two review authors independently extracted the efficacy and adverse event data, and examined issues of study quality. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts, at least 200 participants in the comparison, 8 to 12 weeks duration, parallel design); second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison; and third tier from data involving small numbers of participants and considered very likely to be biased or that used outcomes of limited clinical utility, or both., Main Results: Five studies treated 177 participants with painful diabetic neuropathy (104) or postherpetic neuralgia (73). The mean or median ages in the studies were 55 to 72 years. Four studies used a cross-over, and one a parallel group design; 145 participants were randomised to receive desipramine 12.5 mg to 250 mg daily, with most taking 100 mg to 150 mg daily following titration. Comparators were placebo in three studies (an 'active placebo' in two studies), fluoxetine, clomipramine (one study each), and amitriptyline (two studies), and treatment was for two to six weeks. All studies had one or more sources of potential major bias.No study provided first or second tier evidence for any outcome. No data were available on the proportion of people with at least 50% or 30% reduction in pain, but data were available from three studies for our other primary outcome of Patient Global Impression of Change, reported as patient evaluation of pain relief that was 'complete' or 'a lot'. No pooling of data was possible, but third tier evidence in individual studies indicated some improvement in pain relief with desipramine compared with placebo, although this was very low quality evidence, derived mainly from group mean data and completer analyses in small, short duration studies where major bias was possible. There were too few participants in comparisons of desipramine with another active treatment to draw any conclusions.All studies reported some information about adverse events, but reporting was inconsistent and fragmented. Participants taking desipramine experienced more adverse events, and a higher rate of withdrawal due to adverse events, than did participants taking placebo (very low quality evidence)., Authors' Conclusions: This review found little evidence to support the use of desipramine to treat neuropathic pain. There was very low quality evidence of benefit and harm, but this came from studies that were methodologically flawed and potentially subject to major bias. Effective medicines with much greater supportive evidence are available. There may be a role for desipramine in patients who have not obtained pain relief from other treatments.

We aimed to determine clinical effectiveness of pharmacological interventions for self-injurious behaviour in adults with intellectual disability. We searched the following databases: CENTRAL; MEDLINE; EMBASE; PsycINFO; CINAHL; SCI; SSCI; Conference Proceedings Citation Index - Science; Conference Proceedings Citation Index - Social Science and Humanities; ZETOC; World Cat .We also searched ClinicalTrials.gov,ICTRP and the reference lists of included trials. We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour. We found five double-blind, placebo-controlled trials, which included a total of 50 people. Four trials compared the effects of naltrexone versus placebo and one trial clomipramine versus placebo. We did not identify any relevant placebo-controlled trials for other drugs. We presented a narrative summary, as meta-analysis was not appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures. There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating self-injurious behaviour. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo., (© The Author(s) 2014.)

Our aim was to investigate the impact of comorbid body dysmorphic disorder (BDD) on the response to sequential pharmacological trials in adult obsessive-compulsive disorder (OCD) patients. The sequential trial initially involved fluoxetine monotherapy followed by one of three randomized, add-on strategies: placebo, clomipramine or quetiapine. We included 138 patients in the initial phase of fluoxetine, up to 80 mg or the maximum tolerated dosage, for 12 weeks. We invited 70 non-responders to participate in the add-on trial; as 54 accepted, we allocated 18 to each treatment group and followed them for an additional 12 weeks. To evaluate the combined effects of sex, age, age at onset, initial severity, type of augmentation and BDD on the response to sequential treatments, we constructed a model using generalized estimating equations (GEE). Of the 39 patients who completed the study (OCD-BDD, n = 13; OCD-non-BDD, n = 26), the OCD-BDD patients were less likely to be classified as responders than the OCD-non-BDD patients (Pearson Chi-Square = 4.4; p = 0.036). In the GEE model, BDD was not significantly associated with a worse response to sequential treatments (z-robust = 1.77; p = 0.07). The predictive potential of BDD regarding sequential treatment strategies for OCD did not survive when the analyses were controlled for other clinical characteristics., (© The Author(s) 2013.)

Narcolepsy, one of the important causes of hypersomnia, is an under diagnosed sleep disorder. It has a bimodal age of onset around 15 and 35 years. It is characterized by the tetrad of excessive daytime sleepiness, cataplexy, hypnagogic/ hypnopompic hallucinations, and sleep paralysis. Cataplexy is by far the most predictive feature of narcolepsy. Status cataplecticus is the occurrence of cataplexy repeatedly for hours or days, a rare presentation of narcolepsy. This report describes an elderly gentleman with late onset narcolepsy in the sixth decade of life presenting with initial and chief symptom of status cataplecticus.

Compulsive behaviors in patients with behavioral variant frontotemporal dementia (bvFTD) occur frequently and are challenging to manage. We report three cases of probable bvFTD associated with compulsive behaviors that responded well to treatment with clomipramine at daily dosages varying from 20 to 175 mg. The titration approach involved an initial 10-mg dose that was subsequently increased in 10 mg increments on a weekly basis until symptom relief without intolerable side effects. Our case series supports the consideration for a therapeutic trial with clomipramine in bvFTD when compulsive behavior occurs in these patients. It also highlights the need for further research on pharmacological treatments in bvFTD.

Background: The drug treatments of choice for obsessive-compulsive disorder (OCD) are serotonin reuptake inhibitors (SRIs). However, a correlation between the neuropeptide oxytocin in cerebrospinal fluid and the severity of OCD has previously been shown, and oxytocin and serotonin are interconnected within the brain. Few studies have investigated whether SRIs have any effect on oxytocin; thus, our aim was to explore the possibility that oxytocinergic mechanisms contribute to the anti-obsessive effect of SRIs., Method: In a randomized, double-blind trial, comparing SRIs (clomipramine and paroxetine) with placebo in 36 adults with OCD (characterized for subtypes), plasma oxytocin was measured with radioimmunoassay after plasma extraction, at baseline, after 1 week, and after 4 weeks of treatment, and related to baseline severity and clinical response after 12 weeks, as measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS)., Results: Baseline oxytocin levels correlated positively with baseline Y-BOCS ratings, but only among the future SRI responders. Patients with early onset of OCD had higher baseline oxytocin. During treatment, plasma oxytocin did not differ between SRI and placebo treatment. In SRI responders, plasma oxytocin first decreased and then increased; in non-responders (to SRI as well as to placebo), the reverse was the case. After 4 weeks, treatment responders had attained higher oxytocin levels compared to non-responders. The intra-individual range (i.e., the variability) of plasma oxytocin between measurements was the measure that best differentiated responders from non-responders. This range was higher in responders than non-responders, and lower in patients with autistic traits., Conclusions: SRIs have highly variable effects on plasma oxytocin between individuals. The associations between baseline oxytocin and OCD severity and between oxytocin changes and treatment response support the notions that oxytocin is involved in OCD pathophysiology, and that the anti-obsessive effects of SRIs are partly exerted through oxytocinergic mechanisms.

Background: Trigeminal neuralgia was defined by the International Association for the Study of Pain as a sudden, usually unilateral, severe, brief, stabbing recurrent pain in the distribution of one or more branches of the fifth cranial nerve. Standard treatment is with anti-epileptic drugs. Non-antiepileptic drugs have been used in the management of trigeminal neuralgia since the 1970s. This is an update of a review first published in 2006 and previously updated in 2011., Objectives: To systematically review the efficacy and tolerability of non-antiepileptic drugs for trigeminal neuralgia., Search Methods: On 20 May 2013, for this updated review, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 4), MEDLINE (January 1966 to May 2013), EMBASE (January 1980 to May 2013), LILACS (January 1982 to May 2013) and the Chinese Biomedical Retrieval System (1978 to May 2013). We searched clinical trials registries for ongoing trials., Selection Criteria: We included double-blind, randomised controlled trials in which the active drug was used either alone or in combination with other non-antiepileptic drugs for at least two weeks., Data Collection and Analysis: Two authors decided which trials fitted the inclusion criteria and independently graded risk of bias. We assessed the quality of the evidence according to the GRADE criteria for this update., Main Results: In this 2013 update, we updated the searches, but identified only two new ongoing studies. The review includes four trials involving 139 participants. The primary outcome measure in each was pain relief. Three trials compared one of the oral non-antiepileptic drugs tizanidine, tocainide or pimozide with carbamazepine. The quality of evidence for all outcomes for which data were available was low. In a trial of tizanidine involving 12 participants (one dropped out due to unrelated disease), one of five participants treated with tizanidine and four of six treated with carbamazepine improved (risk ratio (RR) 0.30, 95% confidence interval (CI) 0.05 to 1.89). Few side effects were noted with tizanidine. For pimozide, there was evidence of greater efficacy than carbamazepine at six weeks. Up to 83% of participants reported adverse effects but these did not lead to withdrawal; the report did not provide comparable data for carbamazepine. Limited data meant that we could not assess the effects of tocainide; however, data from non-randomised studies (not included in this review) indicate that serious haematological adverse events can occur. A trial involving 47 participants compared 0.5% proparacaine hydrochloride eyedrops with placebo but did not show any significant benefits, again according to low-quality evidence. The report did not mention adverse events. The proparacaine trial was at low risk of bias; the other trials were at unclear risk of bias overall., Authors' Conclusions: There is low-quality evidence that the effect of tizanidine is not significantly different than that of carbamazepine in treating trigeminal neuralgia. Pimozide is more effective than carbamazepine, although the evidence is of low quality and the data did not allow comparison of adverse event rates. There is also low-quality evidence that 0.5% proparacaine hydrochloride eye drops have no benefit over placebo. Limitations in the data for tocainide prevent any conclusions being drawn. There is insufficient evidence from randomised controlled trials to show significant benefit from non-antiepileptic drugs in trigeminal neuralgia. More research is needed.

Objective: The purpose of this study was to test the efficacy of clomipramine and fluoxetine, controlled by placebo, and compare their action in children and adolescents with anxiety disorders., Method: Thirty subjects (ages 7-17 years), who were diagnosed with generalized anxiety disorder and/or separation anxiety disorder and/or social phobia, were submitted to a 12 week double-blind, randomized, placebo-controlled trial of clomipramine and fluoxetine. The instruments included: the Schedule for Affective Disorders and Schizophrenia, the Multidimensional Anxiety Scale for Children, the Children's Depression Inventory, the Clinical Global Impressions, and the Children's Global Assessment Scale., Results: All groups (clomipramine [n=9], fluoxetine [n=10], placebo [n=11]) showed a significant improvement after 12 weeks of treatment. There were significant differences between the fluoxetine and placebo groups in some ratings of anxiety severity and impairment. No significant differences were observed between clomipramine and placebo groups or between fluoxetine and clomipramine groups., Conclusions: Treatment with placebo showed an unusual high response rate. Clomipramine showed similar efficacy compared with fluoxetine, although it was not superior to placebo.

Background: Trichotillomania (TTM) (hair-pulling disorder) is a prevalent and disabling disorder characterised by recurrent hair-pulling. The effect of medication on trichotillomania has not been systematically evaluated., Objectives: To assess the effects of medication for trichotillomania in adults compared with placebo or other active agents., Search Methods: We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register (to 31 July 2013), which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). Two review authors identified relevant trials by assessing the abstracts of all possible studies., Selection Criteria: We selected randomised controlled trials (RCTs) of a medication versus placebo or active agent for TTM in adults., Data Collection and Analysis: Two review authors independently performed the data extraction and 'Risk of bias' assessments, and disagreements were resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of trichotillomania symptoms on a continuous measure of trichotillomania symptom severity, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CIs)., Main Results: We identified eight studies with a total of 204 participants and a mean sample size of 25. All trials were single-centre trials, and participants seen on an outpatient basis. Seven studies compared medication and placebo (n = 184); one study compared medication and another active agent (n = 13). Duration of the studies was six to twelve weeks. Meta-analysis was not undertaken because of the methodological heterogeneity of the trials. The studies did not employ intention-to-treat analyses and were at a high risk of attrition bias. Adverse events were not well-documented in the studies.None of the three studies of selective serotonin reuptake inhibitors (SSRIs) demonstrated strong evidence of a treatment effect on any of the outcomes of interest. The unpublished naltrexone study did not provide strong evidence of a treatment effect. Two studies, an olanzapine study and a N-acetylcysteine (NAC) study, reported statistically significant treatment effects. One study of clomipramine demonstrated a treatment effect on two out of three measures of response to treatment., Authors' Conclusions: No particular medication class definitively demonstrates efficacy in the treatment of trichotillomania. Preliminary evidence suggests treatment effects of clomipramine, NAC and olanzapine based on three individual trials, albeit with very small sample sizes.

Objective: Aquagenic pruritus is the development of severe, prickling-like skin discomfort without observable skin lesions that is evoked by contact with water at any temperature., Method: This is a case report of a man presenting with aquagenic pruritus after starting clomipramine treatment for anxiety and depression., Results: The patient's aquagenic pruritus resolved after discontinuing the clomipramine but reemerged when treatment was restarted., Conclusions: A greater awareness and knowledge about aquagenic pruritus among physicians could help improve the clinical recognition and management of this clinical entity., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: There is growing evidence that memantine, a noncompetitive N-methyl-D-aspartate receptor antagonist, may be applied as an add-on in treating patients suffering from obsessive-compulsive disorders (OCD). The aim of the present study was therefore to assess the effect of adjuvant memantine in a double-blind, randomized, and placebo-controlled study of the treatment of patients suffering from OCD., Method: A total of 40 inpatients (32 females (80 %); mean age = 31.25 years) suffering from OCD were randomly assigned to a treatment (administration of memantine) or a control group (placebo). Treatment lasted for 12 consecutive weeks. All patients were treated with selective serotonin re-uptake inhibitors or clomipramine. Patients completed the Yale-Brown Obsessive Compulsive Scale four times. Experts' ratings consisted in clinical global impression (clinical global impressions (CGI), illness severity and illness improvement; two to three times). Liver enzymes SGOT and SGPT were also assessed (twice)., Results: Of the 40 inpatients approached, 29 completed the 12 consecutive weeks of the study. Of the 11 dropouts, 6 were in the target group and five in the control group. Symptoms significantly decreased across the period of the study, but particularly in the treatment compared with the control group (significant time × group interaction). Illness severity (CGI severity) also significantly decreased over time but more so in the treatment than in the control group (significant time × group interaction). Illness improvements (CGI improvements) were not significant., Conclusions: The pattern of results from the present double-blind, randomized, and placebo-controlled study for the treatment of patients suffering from OCD suggests that adjuvant memantine does significantly and favorably impact on OCD.

Obsessive-compulsive disorder (OCD) is common and associated with marked impairment and reduced quality of life. In the general practitioner's office as well as in the specialist's consultation, patients with OCD usually present intrusive thoughts (obsessions) and repetitive behaviours (compulsions). OCD sufferers generally recognize their obsessions and compulsions as irrational. Without treatment, OCD often takes a chronic course. Some basic aspects can help to identify patients suffering from OCD earlier and to initiate sufficient therapy. With evidence-based treatment with cognitive-behavioral therapy and adequate psychopharmacotherapy, many patients can achieve complete symptom remission. Initial treatment can be initiated in the general practitioner's office.

Objective: Trichobezoar, a hair ball in the gastrointestinal tract, is usually the result of the urge to pull out one's own hair (trichotillomania) and swallow it (trichophagia). It is almost exclusively seen in young females and may cause serious medical complications. This case report will describe an adult female patient with recurrent trichobezoars., Method: Data for this case report was collected from peer-reviewed literature and treatment encounters by the consultation-liaison psychiatry unit; subsequent to obtaining informed consent., Results: The personality characteristics, familial structure and domestic stress found in this case mirror the literature. We initiated behavioral interventions including habit reversal training and patient education in combination with pharmacologic therapy with clomipramine., Conclusion: Left untreated, trichophagia can cause a life-threatening emergency, requiring surgery. Recurrence of tichobezoars can be anticipated when the underlying emotional disorder is not addressed using multimodal management including psychiatric evaluation and treatment combined with surgical procedures., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: In animal models of neuropathic pain, the noradrenergic descending pain inhibitory pathways from the locus coeruleus (LC) may be suppressed. However, no study has investigated the correlation between noradrenaline (NA) release in the LC and efficacy of analgesics in rats with painful diabetic neuropathy. Using microdialysis and analysis of mechanical hypersensitivity, we investigated the correlation between NA release in the LC and efficacy of morphine, tramadol, and clomipramine in rats with diabetic mellitus (DM)., Main Methods: In freely moving rats, basal NA concentrations in LC perfusate were quantitated 72 to 96 h after microdialysis probe implantation. Following intravenous administration of each drug, NA concentrations were expressed as a percentage of basal values. We concurrently measured the threshold to elicit a paw withdrawal response every 20 min for 80 min., Key Findings: NA concentrations in the LC perfusate were significantly higher in the tramadol and clomipramine groups compared to the morphine group. Naloxone administration did not significantly affect NA concentrations. In the morphine group, NA release in the LC was not significantly correlated with the pain threshold. In contrast, in the tramadol and clomipramine groups, NA release in the LC was significantly correlated with the pain threshold. The correlation coefficient was higher in the clomipramine group than in the tramadol group., Significance: Our results suggest that the descending noradrenergic pathway can play an important role in analgesia for DM neuropathy and that there is a significant correlation between NA release in the LC and the efficacy of tramadol and clomipramine., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: We compared citalopram and clomipramine against placebo with respect to recurrence prevention as opposed to relapse prevention in patients with recurrent depression, independently of any acute response to the test drug(s)., Methods: Patients with recurrent depressive disorder with a current depressive episode of moderate to severe degree were recruited over a period of 6.5 years. After 6-15 months of routine open acute and continuation therapy, and a discontinuation/drug-free period of one month following sustained response (at least 3 consecutive monthly ratings with a HAM-D-17-score below 13), patients were randomised under double-blind conditions, with a follow-up period of 2 years. The major endpoint was recurrence (HAM-D-17-score of 16 or above)., Results: A total of 307 patients were included in the open phase and 174 patients completed at least 6 months of treatment and achieved sustained response. Out of these, only 59 patients (34%) could be randomised to placebo (n=22), citalopram (n=19) or clomipramine (n=22), with protocol violation and/or non-consent being the major reasons for non-randomisation. There were no between-group differences in outcome; almost half of the randomised patients met the criterion for recurrence., Limitations: The size of the randomised sample was considerably smaller than the planned size., Conclusions: The high risk of drop out prior to randomisation among the eligible patients was presumably caused by an interaction between the study design and the study population. The findings suggest that long-term trial designs interposing a drug-free period prior to randomisation are not feasible and recommendable in severely ill patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimental Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. Infected mice were treated with CLO 5mg/kg/day and BZN 50 and 100mg/kg/day, each separately or together. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopathological studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly (P<0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The lower dose of BZN (50mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of BZN (100mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO presented lesser side effects than the treatment with BZN., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Self-injurious behaviour among people with intellectual disability is relatively common and often persistent. Self-injurious behaviour continues to present a challenge to clinicians. It remains poorly understood and difficult to ameliorate despite advances in neurobiology and psychological therapies. There is a strong need for a better evidence base in prescribing and monitoring of drugs in this population, especially since none of the drugs are actually licensed for self-injurious behaviour., Objectives: To determine clinical effectiveness of pharmacological interventions in management of self-injurious behaviour in adults with intellectual disability., Search Methods: We searched the following databases on 19 February 2012: CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL, Science Citation Index, Social Science Citation Index, Conference Proceedings Citation Index - Science, Conference Proceedings Citation Index - Social Science and Humanities, ZETOC and WorldCat. We also searched ClinicalTrials.gov, ICTRP and the reference lists of included trials., Selection Criteria: We included randomised controlled trials that examined drug interventions versus placebo for self-injurious behaviour (SIB) in adults with intellectual disability., Data Collection and Analysis: Two review authors independently extracted data and assessed risk of bias for each trial using a data extraction form. We present a narrative summary of the results is presented. We did not consider meta-analysis was appropriate due to differences in study designs, differences between interventions and heterogeneous outcome measures., Main Results: We found five double-blind placebo-controlled trials that met our inclusion criteria. These trials assessed effectiveness and safety of drugs in a total of 50 people with intellectual disability demonstrating SIB. Four trials compared the effects of naltrexone versus placebo and one trial compared clomipramine versus placebo.One of the naltrexone versus placebo trials reported that naltrexone had clinically significant effects (≥ 33% reduction) on the daily rates of three of the four participants' most severe form of SIB and modest to substantial reductions in SIB for all participants; however, this study did not report on statistical significance. Another trial reported that naltrexone attenuated SIB in all four participants, with 25 mg and 50 mg doses producing a statistically significant decrease in SIB (P value < 0.05). Another trial (eight people) indicated that naltrexone administration was associated with significantly fewer days of high frequency self injury and significantly more days with low frequency self injury. Naltrexone had different effects depending on the form and location of self injury. Another trial with only 26 participants found that neither single-dose (100 mg) nor long-term (50 and 150 mg) naltrexone treatment had any therapeutic effect on SIB.Comparison of clomipramine versus placebo found no statistically significant benefit for any outcome measure, which included SIB rate and intensity, stereotypy and adverse events. However, it showed clinically significant improvement in the rate and intensity of SIB and stereotypy.There were very few noteworthy adverse events to report in any of the four trials in which these were reported.All trials were at high risk of bias, apart from one trial (Lewis 1996), which was probably at low risk of bias. The short period of follow-up was a significant drawback in the design of all five trials, as it did not allow long-term assessment of behaviour over time.We were unable to examine the efficacy of antidepressants other than clomipramine, antipsychotics, mood stabilisers or beta-blockers as we did not identify any relevant placebo-controlled trials., Authors' Conclusions: There was weak evidence in included trials that any active drug was more effective than placebo for people with intellectual disability demonstrating SIB. Due to sparse data, an absence of power and statistical significance, and high risk of bias for four of the included trials, we are unable to reach any definite conclusions about the relative benefits of naltrexone or clomipramine compared to placebo.

An increased vulnerability to pain complaints, along with a simultaneous increase in experimental pain thresholds, shows the paradoxical phenomenon of pain perception in depressive patients. Clomipramine, a tricyclic antidepressant, could also ameliorate syndromes in chronic pain patients. However, few studies have focused on the effect of antidepressants on experimental pain thresholds. By using a rat model, the learned helplessness paradigm, the present study explored the effect of clomipramine on behavioral deficits and experimental pain thresholds to different stimuli in "helpless" rats. Helpless rats were administered clomipramine (10mg/kg, i.p, b.i.d.) for 5 consecutive days. The depressive-like and anxiety-like behaviors were detected by shuttle box, open field and elevated plus maze test before and after inescapable shock and after medication. The sensitivity to the thermal and mechanical stimuli was also measured by the von Frey hair and Hargreaves test at the indicated time points. Helpless rats displayed shorter total travel distance and fewer rearing times in the open field test and decreased percentage of time spent in the open arms in the elevated plus maze test. In addition, they exhibited significant hypoalgesia/hypoesthesia to mechanical and thermal stimuli. Clomipramine alleviate depressive-like and anxiety-like behaviors and increased the sensitivity to von Frey filament stimuli with no effect on the sensitivity to radiant heat stimuli in helpless rats. These suggested that clomipramine could reverse mechanical but not thermal hypoalgesia/hypoesthesia and simultaneously improved behavioral deficits., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder associated with a significant degree of functional disability and poor quality of life. Pharmacotherapy may have a substantial impact on the course and outcome of OCD., Method: We review the evidence supporting available strategies for the pharmacological treatment of OCD., Results: Selective serotonin reuptake inhibitors (SSRIs) remain the pharmacological treatment of choice and are associated with improved health-related quality of life. Discontinuation is associated with relapse and loss of quality of life, implying treatment should continue long-term. A substantial minority of patients who fail to respond to SSRI may benefit from dose elevation or adjunctive antipsychotics, though long-term trials validating the effectiveness and tolerability of these strategies are relatively lacking., Conclusion: The pharmacological evidence-base for the treatment of OCD is becoming increasingly robust. Treatment with SSRIs and clomipramine remains uncontroversial and improvements are sustained over time. Newer compounds targeting serotonin receptor subtypes and other neurotransmitter systems are undergoing evaluation.

The protective effects of St John's Wort extract (SJ), ginsenosides (GS), and clomipramine (CPM) on chronic unpredictable mild stress (CUMS)-induced depression in rats were investigated by using a combination of behavioral assessments and metabonomics. Metabonomic analyses were performed using gas chromatography/mass spectrometry in conjunction with multivariate and univariate statistical analyses. During and at the end point of the chronic stress experiment, food consumption, body weight, adrenal gland, thymus and spleen indices, behavior scores, sucrose consumption, and stress hormone levels were measured. Changes in these parameters reflected characteristic phenotypes of depression in rats. Metabonomic analysis of serum, urine, and brain tissue revealed that CPM and SJ mainly attenuated the alteration of monoamine neurotransmitter metabolites, while GS affected both excitatory/inhibitory amino acids and monoamine neurotransmitter metabolites. GS also attenuated the stress-induced alterations in cerebrum and peripheral metabolites to a greater extent than CPM and SJ. These results provide important mechanistic insights into the protective effects of GS against CUMS-induced depression and metabolic dysfunction.

Objective: To investigate to what extent the primary depression subtype atypical depression can predict differential outcome of the mono-amino-oxidase inhibitor (MAO-I) moclobemide and the tricyclic antidepressant clomipramine in the Danish University Antidepressant Group Study (DUAG)., Methods: In a randomised, double blind trial, a total of 117 patients with major depression were treated over 6 weeks with either 400 mg moclobemide or 150 mg clomipramine. A baseline principal component analysis (PCA) was performed to identify atypical symptoms on the combined depression scales (Hamilton Depression Scale (HAM-D(17)) and the Quantitative Scale for Atypical Depression (QSAD)). The primary outcome scale was the subscale HAM-D(6) which contains the pure items of depression., Results: PCA identified two items with loadings opposite to the other depression items within HAM-D(17) and QSAD, namely increased duration of sleep and increased appetite (atypical neurovegetative symptoms). Patients with a positive score at baseline on these items were classified as having atypical depression. In total 13 patients were classified as having atypical depression. Within this group of patients 8 received clomipramine and 5 patients received moclobemide. At endpoint the moclobemide treated patients had a significantly better response than the clomipramine treated (P=0.036), effect size 1.42, when using HAM-D(6) as outcome. However, in the 104 patients classified as having typical depression clomipramine was superior to moclobemide (P=0.034), effect size 0.47., Limitations: The number of patients with atypical neurovegetative symptoms was very small and no placebo arm was included., Conclusions: It is very important to screen for atypical depression (increased duration of sleep/increased appetite) in the acute therapy of patients with major depression. Our results add to the body of evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants in this sub-group of patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Recently it was revealed that the absence-like epileptic activity of the WAG/Rij (Wistar Albino Glaxo/Rijswijk) rat is associated with depression-like behavioural symptoms. Whether these depressive-like symptoms are accompanying epileptic activity (manifested in spike-wave discharges, SWDs, in the EEG) or whether they are causative for each other are open questions. Neonatally administered tricyclic antidepressant clomipramine is a well characterized animal model of major depression. It evokes behavioural symptoms of depression and changes sleep pattern in normal adult rats. We investigated whether in the WAG/Rij rat the neonatally administered clomipramine would aggravate the depression-like behavioural symptoms and the SWD activity. Male WAG/Rij pups from postnatal day 8 (PD8) to PD21 were treated with clomipramine (20mg/kg) or saline (control animals) twice daily intraperitoneally (i.p.). In the 8 months old rats, sleep parameters and sucrose solution intake (as hedonic index) as well as the SWD activity were measured. While the neonatal clomipramine treatment significantly increased the rapid eye movement sleep (REM) amount and decreased the sucrose preference score, it surprisingly attenuated the adult (8 months old) SWD activity. We concluded that neonatal clomipramine treatment produced aggravation of depression-like symptoms while decreased the SWD activity in the adult (8 months old) WAG/Rij rat., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Despair-related withdrawal behaviors are common symptoms of major depression (MD) and can be ascribed to a loss or absence of former rewarding events. Extinction of negatively reinforced escape behavior in the Morris Water Maze has been shown to induce despair-like behavior. A new animal model of depressive-like behavior is based on the extinction of positively reinforced behavior, which was shown to induce spatial avoidance of the former source of reward and biting of the operandum. Treatment with antidepressants attenuated these extinction-induced behaviors, suggesting that they reflect a depressive-like state. Here we present a methodological variation of this depression model. We employed an elongated operant chamber rather than a two-compartment procedure with the intent to establish a flowing gradient of withdrawal from the source of reward, rather than an all-or-none binary measure. Furthermore, instead of employing extinction of lever-pressing behavior, we applied a cued fixed-time food-delivery schedule. Sixty adult male Wistar rats (n=12/group) were trained to receive a food reward after appearance of a cue-light (fixed interval 90s) in an elongated Skinner-box of 72 cm length. Prior to extinction, the animals were treated for 9 days with either 7.5 or 10mg/kg of the tricyclic antidepressant clomipramine, 7.5 or 10mg/kg of the selective serotonin reuptake inhibitor (SSRI) citalopram or vehicle. Subsequent testing in an open field was carried out to investigate potential effects of the antidepressants on locomotor- and anxiety-like behavior. An overall increase in distance from the feeder and biting behavior was found over the course of the extinction trials. Both, citalopram and clomipramine decreased the distance from the pellet feeder during the initial extinction trials compared to the vehicle-treated group. The attenuation of withdrawal behavior by the antidepressants supports the hypothesis that avoidance/withdrawal behavior during extinction trials can serve as a marker for extinction-induced depression and suggests the utility of this paradigm as a rodent model of depression., (Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Compulsivity is the repetitive, irresistible urge to perform a behavior, the experience of loss of voluntary control over this intense urge and the tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is part of obsessive-compulsive disorder (OCD), but may occasionally occur as stand-alone symptom following brain damage induced by cardiac arrest. In this case report, we describe a patient who developed compulsivity following cardiac arrest. We review diagnostic options, underlying mechanisms and possible treatments., Case Presentation: A 65-year-old man presented at our clinic with continuous compulsive whistling following cardiac arrest. Neither obsessive-compulsive symptoms, nor other psychiatric complaints were present prior to the hypoxic incident. An EEG showed diffuse hypofunction, mainly in baso-temporal areas. Treatment with clomipramine resulted in a decrease of whistling., Discussion: This case report illustrates de novo manifestation of compulsivity following cardiac arrest and subsequent brain damage and gives additional information on diagnostic options, mechanisms and treatment options. Differential diagnosis between stereotypies, punding, or OCD is difficult. Compulsivity following brain damage may benefit from treatment with serotonin reuptake inhibitors. This finding enhances our knowledge of treatments in similar cases.

Narcolepsy is an emblematic, unique disease within sleep disorders that is characterised by excessive daytime sleepiness, cataplexy and other abnormal manifestations of REM sleep. In the last 14 years truly spectacular progress has been made in our knowledge of this disease, since the discovery of its cause, i.e. a loss of the hypothalamic neurons that synthesise hypocretin, a previously unknown neurotransmitter, and its probable aetiopathogenic mechanisms, i.e. an autoimmune process in a patient with very precise immunological characteristics - a specific type of HLA and a specific type of T-cell receptor. The cause of this autoimmune process remains unknown. The definitive treatment - the administration of hypocretin, which is the substance missing in the organism - is still unavailable, but there are powerful drugs for treating its main symptoms, the sleepiness and the cataplexy. Some of these are classic compounds (methylphenidate, clomipramine), while others are more recent (modafinil, venlafaxine, sodium oxybate), but together they allow many patients to experience significant improvements. Lack of knowledge about the disease, both on the part of patients and their relatives as well as physicians, is the reason for the great delay in its diagnosis, with even more dramatic consequences when the disease begins in infancy.

Background: Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders, ranging in severity and characterised by early onset of delay and deviance in the development of social interaction, and verbal and nonverbal communication. ASD is associated with restricted and/or stereotyped interests or behaviours. Tricyclic antidepressants (TCAs) block noradrenaline and serotonin reuptake, increasing the availability of these neurotransmitters in the central nervous system. Via their impact on serotonin, TCAs have been used in the treatment of autistic symptoms and comorbidities in individuals with ASD.  , Objectives: To determine if treatment with tricyclic antidepressants:1) improves the core features of autism, including restricted social interaction, restricted communication, and stereotypical and repetitive behaviours; 2) improves non-core features such as challenging behaviours; 3) improves comorbid states, such as depression and anxiety; 4) causes adverse effects., Search Methods: We ran the latest searches for this review on 23 May 2011. We searched: Cochrane Central Register of Controlled Trials (CENTRAL), 2011 Issue 2, MEDLINE (1948 to May Week 2, 2011), EMBASE (1980 to 2011 Week 2), PsycINFO (1887 to current), CINAHL (1937 to current). We also searched Dissertation Abstracts International via Dissertation Express, and the metaRegister of Controlled Trials., Selection Criteria: Randomised controlled trials of any dose, duration and frequency of oral TCAs compared with placebo, in children and adolescents with a diagnosis of ASD, where at least one standardised outcome measure had been used., Data Collection and Analysis: Two review authors independently selected and appraised the studies for inclusion and risk of bias. All data were continuous., Main Results: Three studies met the inclusion criteria for this review. Two studies used clomipramine and one used tianeptine. All three trials were small, with between 12 and 32 participants. One of the clomipramine trials involved children and young adults, while the other two trials enrolled only children. Due to heterogeneity in study participant characteristics, the TCA medications investigated and the outcome measures used, we were not able to perform any meta-analysis.In only one of the three studies was there any indication that giving children tianeptine could be effective in the short term. In this study, parents and teachers reported that it reduced irritability, hyperactivity, inadequate eye contact and inappropriate speech, but clinician ratings found no significant impact on these symptoms. There were also significant adverse effects, including increased drowsiness and reduced activity levels in these individuals while being treated with tianeptine. The evidence of the impact of clomipramine in the two studies is contradictory. There was evidence of improvement in autistic symptoms, irritability and obsessive-compulsive disorder type symptoms, but conflicting evidence in relation to hyperactivity across the two studies, and no significant changes found with inappropriate speech. There were also adverse effects reported with the use of clomipramine. Although side effect ratings were not significantly different to placebo, there were significant dropout rates in the clomipramine arm of one study., Authors' Conclusions: Clinicians considering the use of TCAs need to be aware of the limited and conflicting evidence of effect and the side effect profile when discussing this treatment option with people who have ASD and their carers. Further research is required before TCAs can be recommended for treatment of individuals with ASD.

Background: Body dysmorphic disorder (BDD) has been described widely in the Western world as relatively common yet under-recognized, but rarely in Africans and none in Nigeria to the best of our knowledge., Aim: To report a case of BDD in a Nigerian boy presenting with depression to the psychiatric unit of a teaching hospital., Method: A 17-year-old secondary school boy with BDD presenting with depression is reported and relevant literature is reviewed., Conclusion: BDD is rare and hardly reported in this environment and high index of suspicion is necessary in patient presenting with medically unexplained physical complaints and depression.

Cognitive-behavioral therapy (CBT) and pharmacological treatments are often applied in cases of pediatric obsessive-compulsive disorder (OCD). Especially in combination both methods are particularly efficacious; nonetheless, 40 % of all patients treated remain symptomatic. Exposure with response prevention, based on the principle of habituation, is the intervention with the best evidence. More recent cognitive and metacognitive treatments focus on modifying expectations and may have the potential to improve treatment efficacy. Selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment in severe cases of OCD. With treatment resistance, the SSRI should be changed, or alternatively clomipramine can be employed. Augmentation strategies suggest the combination of two SSRIs, SSRI und clomipramin, or SSRI and (atypical) neuroleptics. Following successful treatment, medication should be reduced very slowly. Novel treatments in children and adolescent have been reported for antiglutamatergic agents as riluzole or D-cycloserine, a partial agonist of N-methyl-D-aspartic acid (NMDA).

Anxiety disorders represent the most prevalent psychiatric disorders. In addition, a considerable burden is associated with them, not only for individual sufferers, but also for the health care system. However, many patients who might benefit from treatment are not diagnosed or treated. This may partly be due to lack of awareness of the anxiety disorders by primary care practitioners and by the sufferers themselves. In addition, the stigma still associated with psychiatric disorders and lack of confidence in psychiatric treatments are factors leading to no/under recognition and treatment, or the use of unnecessary or inappropriate treatments. This paper aims to provide a comprehensive review of recommendations for the pharmacological treatment of two common anxiety disorders, in particular obsessive-compulsive disorder (OCD) and panic disorder (PD). The first-line treatments of OCD include medium-high doses of selective serotonin reuptake inhibitors (SSRIs) and clomipramine, a tricyclic (TCA) antidepressant with prevalent serotonergic activity. The recommended drugs for PD include SSRIs, TCAs and serotonin-norepinephrine reuptake inhibitors (SNRIs); in treatment-resistant cases, benzodiazepines like alprazolam may be used in patients with no history of addiction and tolerance. Other treatment options include irreversible and reversible monoamine-oxidase inhibitors, hydroxyzine, and others. Besides pharmacological treatments, some psychological strategies have been shown to be effective, in particular, cognitive behavior therapy (CBT) and other variants of behavior therapy that have been sufficiently investigated in controlled studies, and, therefore, will be reviewed herein.

Premature ejaculation is the most common sexual dysfunction in men. Its prevalence rate in Europe and in United States is estimated to be between 20% and 30%. The diagnosis of premature ejaculation is based on three main criteria: increased intravaginal ejaculatory latency time (IELT), lack of control over ejaculation and interpersonal psychological disturbances. Premature ejaculation is classified as lifelong (primary) or acquired (secondary) and might be facilitated by chronic prostatitis, diabetes mellitus, hyperthyroidism, obesity. The exact etiology of the disease remains unclear, although 5-HT (5-hydroxytryptamine) receptors are known to have a significant role. The use of SSRIs (selective serotonine reuptake inhibitors) is old and efficient form of therapy for premature ejaculation. Other drugs like tramadol, clomipramine, local anaesthetics and PDE-5 (phosphodiesterase 5) inhibitors also have some efficacy in the treatment of premature ejaculation. To minimize adverse effects the "on demand" therapy is preferred to the daily treatment. Simple questionnaires for patients are used to assess treatment effects.

Obsessive-compulsive disorder (OCD) is an anxiety disorder that affects between 1% to 2% of individuals and causes considerable impairment and disability. Although > 50% of individuals experience symptom onset in childhood, symptoms can continue to develop throughout adulthood. Accurate and timely assessment of clinical presentation is critical to limit impairment and improve prognosis. Presently, there are 2 empirically supported treatments available for OCD in children and adults, namely cognitive-behavioral therapy and pharmacotherapy with serotonin reuptake inhibitors. This article provides an introduction to the phenomenology, etiology, and clinical course of OCD. Assessment practices used to evaluate symptom severity are described, and evidence-based treatment options are reviewed, with appropriate distinctions drawn between children and adults. Finally, recommendations for assessment and treatment practices for OCD are explicated.

Obsessive-compulsive disorder patients who do not improve sufficiently after treatment with a selective serotonin reuptake inhibitor might improve further if other drugs were added to the treatment regimen. The authors present a double-blind, placebo-controlled trial comparing the efficacy of adding quetiapine or clomipramine to a treatment regimen consisting of fluoxetine. Between May 2007 and March 2010, a total of 54 patients with a primary diagnosis of obsessive-compulsive disorder, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, and a current Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score of at least 16, the score having dropped by less than 35% after fluoxetine monotherapy, were allocated to 1 of 3 arms (n = 18 per arm): quetiapine + fluoxetine (≤200 and ≤40 mg/d, respectively), clomipramine + fluoxetine (≤75 and ≤40 mg/d, respectively), or placebo + fluoxetine (≤80 mg/d of fluoxetine). Follow-up was 12 weeks. The Y-BOCS scores were the main outcome measure. No severe adverse events occurred during the trial, and 40 patients (74%) completed the 12-week protocol. The Y-BOCS scores (mean [SD]) were significantly better in the placebo + fluoxetine and clomipramine + fluoxetine groups than in the quetiapine + fluoxetine group (final: 18 [7] and 18 [7], respectively, vs 25 [6], P < 0.001) (reduction from baseline: -6.7 [confidence interval {CI}, -9.6 to -3.8; and -6.5 [CI, -9.0 to -3.9], respectively, vs -0.1 [CI, -2.9 to 2.7], P < 0.001; number needed to treat = 2.4). The clomipramine-fluoxetine combination is a safe and effective treatment for fluoxetine nonresponders, especially those who cannot tolerate high doses of fluoxetine. However, the period of monotherapy with the maximum dose of fluoxetine should be extended before a combination treatment strategy is applied.

Background: Perseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following 4 to 8 weeks of treatment. Using mice, we compared the effects of chronic SRI versus NRI treatment on 5-HT1BR-induced OCD-like behavior and 5-HT1BR sensitivity in orbitofrontal-subcortical OCD circuits. Furthermore, we localized the 5-HT1BR population that mediates OCD-like behavior., Methods: Mice chronically received the SRI clomipramine or the NRI desipramine and were examined for 5-HT1BR-induced OCD-like behavior or 5-HT1BR binding and G-protein coupling in caudate putamen, nucleus accumbens, and orbitofrontal cortex. Separate mice were tested for OCD- or depression-like behavior following 4, 14, 21, 28, or 56 days of SRI treatment. Finally, OCD-like behavior was assessed following intra-orbitofrontal 5-HT1BR agonist infusion or intra-orbitofrontal 5-HT1BR antagonist infusion coupled with systemic 5-HT1BR agonist treatment., Results: Effective, but not ineffective, OCD treatments reduced OCD-like behavior in mice with a time course that parallels the delayed therapeutic onset in OCD patients and downregulated 5-HT1BR expression in the orbitofrontal cortex. Intra-orbitofrontal 5-HT1BR agonist infusion induced OCD-like behavior, and intra-orbitofrontal 5-HT1BR antagonist infusion blocked OCD-like effects of systemic 5-HT1BR agonist treatment., Conclusions: These results indicate that orbitofrontal 5-HT1BRs are necessary and sufficient to induce OCD-like behavior in mice and that SRI pharmacotherapy reduces OCD-like behavior by desensitizing orbitofrontal 5-HT1BRs. Our findings suggest an essential role for orbitofrontal 5-HT1BRs in OCD pathophysiology and treatment., (Published by Elsevier Inc.)

The aim of this article was to analyze systematically literature information published in English (between 1966 and January 2011) on the efficacy of antidepressants in pediatric obsessive-compulsive disorder. Data were identified through different databases by using variously combined patterns of search terms. Searches provided 85 articles, excluding duplicates, but only articles reporting primary data on use of antidepressants in this specific disorder were reviewed. Fifty-nine articles were excluded because they did not report primary efficacy data or investigated patients with different psychiatric diagnosis. Twenty-five electronically recognized articles met the inclusion criteria. Two additional studies, available as congress communication, were identified by manually checking the references' list of electronically identified articles. Reviewed studies show several methodological biases (the lack/limited number of long-term trials and head-to-head comparisons and the inclusion of patients who continued different forms of psychotherapy), which make it difficult to individuate the best pharmacological strategy. Despite these limitations, evidence-based information suggests that clomipramine and sertraline, especially for long-term treatments, should be considered as first-choice agents for treating obsessive-compulsive disorder at onset during childhood or adolescence.

Introduction: New diagnostic criteria for lifelong premature ejaculation (PE) have been proposed by the International Society of Sexual Medicine (ISSM), including an intravaginal ejaculatory latency time (IELT) of less than about 1 minute, lack of control over ejaculation, and PE-related distress or bother., Aim: The aim of this study was to review evidence supporting the efficacy and safety of oral agents for the treatment of PE in the context of the new ISSM criteria., Methods: The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT., Main Outcome Measures: The main outcome measure used for this study was a review of the efficacy and safety data of oral agents for PE aligned with ISSM criteria., Results: Since the latest meta-analyses using similar criteria (conducted in 2004 and 2005 for selective serotonin reuptake inhibitors [SSRIs] and phosphodiesterase type 5 [PDE-5] inhibitors, respectively), eight studies evaluated SSRIs vs. placebo, one compared SSRIs, two evaluated PDE-5 inhibitors, and one evaluated an SSRI/PDE-5 inhibitor combination. New agents included dapoxetine (five studies) and tramadol (one study). Six studies enrolled men who met an approximation of the ISSM criteria. Although evidence suggests that most SSRIs, tramadol, and dapoxetine increase IELT to varying degrees, few studies included control over ejaculation and PE-related distress or bother as enrollment criteria or used validated patient-reported outcome instruments to evaluate these parameters. Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e.g., withdrawal syndrome) were not evaluated in men with PE., Conclusions: This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria., (© 2011 International Society for Sexual Medicine.)

Neuropsychiatric conditions are common in patients with primary antiphospholipid syndrome (APS) with or without vascular thrombosis of the central nervous system. There are frequent descriptions of memory alterations, cognition and mood disorders, such as depression, anxiety, and even conditions of mania and psychosis preceding the diagnosis of primary APS. However, this study is the first to present primary or secondary APS associated with habit or impulse control disorders. The authors describe the case of a 53-year-old male patient who had been a pathological gambler since adulthood and who has had APS for more than 20 years. We describe the case and review its characteristics, criteria for diagnosis and treatment offered for patients with this specific subtype of impulse disorder.

Introduction: Mefloquine (Lariam) is the drug of choice as malaria prophylaxis for travel to chloroquine-resistant areas. Severe neuropsychiatric side effects are rare. We report two clinical cases of mood disorders: mania and a major depressive episode with psychotic characteristics in two patients with mefloquine antimalarial prophylaxis. FIRST CLINICAL CASE: A 31-year-old man had taken mefloquine at a rate of 250mg/week as malaria prophylaxis for his mission in Democratic Republic of Congo. He developed mania with psychotic symptoms after taking five tablets of 250mg of mefloquine. He exhibited an elevated mood and also developed delusions of grandeur, reference and persecution, with auditory hallucinations. The physical examination and the blood laboratory tests were normal. The patient was treated with an atypical neuroleptic (olanzapine 20mg/d) leading to a complete resolution of symptomatology at the end of 3 weeks. SECOND CLINICAL CASE: A 27-year-old man presented a major depressive episode with psychotic symptoms after 1 week on his return from a stay in Democratic Republic of Congo, where he had taken mefloquine during 6 months as malaria prophylaxis (250mg/week). His physical examination and investigations (full blood test, serology and MRN) were normal. The patient was treated with clomipramine (150mg/d) and olanzapine (20mg/d). The outcome was favorable after 4 weeks., Discussion: Mefloquine is widely accepted as a safe and effective treatment and a prophylactic agent for chlorquine-resistant malaria. Common neuropsychiatric adverse effects of mefloquine can occur in up to 40% of patients, such as dizziness, sleep disturbances, anorexia, ataxia, and fatigue. Other more serious adverse reactions are rare. They are represented primarily by panic attacks, convulsions, acute psychosis, paranoid delusions, suicidal ideation, disorders of mood: major depressive episode and the manic excitation. The incidence of such neuropsychiatric effects is 1/10,000 to 1/15,000 during the prophylactic treatment. The causal mechanism for the side effects is not known. Several risk factors increasing the neurotoxicity of mefloquine can be identified, the patient with personal or family history of psychiatric disorders are more frequently concerned. Alcohol and the association with other drugs (like quinine) are two other risk factors., Conclusion: It is relevant for medical practitioners to be aware of the severe neuropsychiatric side effects of mefloquine as malaria prophylaxis. It requires investigation of the risk factors such as personal or family history of psychiatric disorders., (Copyright © 2011 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Polymorphisms in genes coding for drug metabolizing enzymes, such as the cytochrome P450 enzymes CYP2C19 and CYP2D6, can lead to therapy failure and side effects. In earlier studies, the novel variant CYP2C19*17 increased metabolism of several CYP2C19 substrates. The objective of this study was to evaluate the impact of CYP2C19*17 on the metabolism of amitriptyline (AT), citalopram (CIT), and clomipramine (CLOM). Six-hundred and seventy-eight patients were included in this study, based on availability of DNA and serum levels of parent drug and main metabolite. We investigated the relationship between CYP2C19 genotypes and metabolic parameters, including serum levels corrected for dose and metabolic ratio (MR). The CYP2C19*17 allele was significantly associated with decreased MR for CIT (CYP2C19*1/*17 mean MR=2.3, compared with CYP2C19*1/*1 mean MR=2.8) and AT (CYP2C19*17/*17 mean MR=0.8, compared with CYP2C19*1/*1 mean MR=3.7 in the CYP2D6*1/*1 subgroup). Furthermore, significant association of CYP2D6 genotype with AT, CIT, and CLOM metabolism was observed. No clear correlation was found between CYP2C19 genotype and CLOM metabolism. This study confirms the increased activity of the CYP2C19*17 allele and shows increased metabolism of drugs that are metabolized by CYP2C19, including AT and CIT. However, the clinical relevance of CYP2C19*17 is probably limited for AT, CIT, and CLOM.

Aims: To develop a behavioral model in mice that is capable of mimicking some distinctive symptoms of human posttraumatic trigeminal neuropathic pain such as spontaneous pain, cold allodynia, and chemical÷inflammatory hyperalgesia, and to use this model to investigate the antinociceptive effects of clomipramine and tramadol, two drugs used for the treatment of neuropathic pain., Methods: A partial tight ligature of the right infraorbital nerve by an intraoral access or a sham procedure was performed. Fourteen days later, mice were subcutaneously injected with saline or drugs and the spontaneous nociceptive behavior, as well as the responses to topical acetone and to formalin or capsaicin injected into the ipsilateral vibrissal pad, were assessed. Data were analyzed by ANOVA., Results: Neuropathic mice exhibited an increased spontaneous rubbing÷scratching of the ipsilateral vibrissal pad, together with enhanced responses to cooling (acetone) and the chemical irritants (formalin, capsaicin). Clomipramine and tramadol produced an antihyperalgesic effect on most of these nociceptive responses, but tramadol was ineffective on capsaicin-induced hyperalgesia., Conclusion: Nociceptive responses in this neuropathic pain model in mice exhibited a pattern consistent with the pain described by posttraumatic trigeminal neuropathic patients. The selective antihyperalgesic effect obtained with two commonly used drugs for treating neuropathic pain confirms the validity of this preclinical model.

We describe a 55-year-old woman with extensive digestive resection and recurrent depressive disorder resistant to oral clomipramine tablets but not to an oral solution of amitriptyline. In the light of this case report, the potential mechanisms of drug resistance after digestive resection are discussed, including the importance of drug monitoring.

A key to advancing the understanding of obsessive-compulsive disorder (OCD)-like symptoms is the development of spontaneous animal models. Over 55 generations of bidirectional selection for nest-building behavior in house mice, Mus musculus, resulted in a 40-fold difference in the amount of cotton used for a nest in high (BIG) and low (SMALL) selected lines. The nesting behavior of BIG mice appears to be compulsive-like and has initial face validity as an animal model for OCD in humans. Compulsive-like digging behavior was assessed; BIG male mice buried about three times as many marbles as SMALL male mice, strengthening face validity. Using the open field and elevated plus maze, SMALL male mice showed higher levels of anxiety/fear-like behavior than BIG male mice, indicating that compulsive-like and not anxiety-like behavior was measured. To establish predictive validity, chronic (4 weeks) oral administration of fluoxetine (30, 50 and 100mg/kg/day) and clomipramine (80 mg/kg/day), both effective in treating OCD, significantly reduced compulsive-like nest-building behavior in BIG male mice. Compulsive-like digging behavior was also significantly reduced by chronic oral fluoxetine (30 and 80 mg/kg/day) treatment in BIG male mice. General locomotor activity was not affected by chronic oral fluoxetine (30 and 80 mg/kg/day) treatment; chronic oral treatment with desipramine (30 mg/kg/day), an antidepressant not effective in treating OCD, had no effect on nesting behavior of BIG male mice, strengthening predictive validity. Together, the results indicate that these mice have good face and predictive validity as a non-induced mouse model of compulsive-like behavior relevant to OCD., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: Several studies have identified discrete symptom dimensions in obsessive-compulsive disorder (OCD), derived from factor analyses of the individual items or symptom categories of the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (YBOCS-SC). This study aims to extend previous work on the relationship between obsessions and compulsions by specifically including mental compulsions and reassurance-seeking. Because these compulsions have traditionally been omitted from prior factor analytic studies, their association to what have been called "pure obsessions" may have been overlooked., Method: Participants (N = 201) were recruited from two multi-site randomized clinical treatment trials for OCD. The YBOCS-SC was used to assess OCD symptoms, as it includes a comprehensive list of obsessions and compulsions, arranged by content category. Each category was given a score based on whether symptoms were present and if the symptom was a primary target of clinical concern, and a factor analysis was conducted. Mental compulsions and reassurance-seeking were considered separate categories for the analysis., Results: Using an orthogonal geomin rotation of 16 YBOCS-SC categories/items, we found a five-factor solution that explained 67% of the total variance. Inspection of items that composed each factor suggests five familiar constructs, with mental compulsions and reassurance-seeking included with sexual, aggressive, and religious obsessions (unacceptable/taboo thoughts)., Conclusions: This study suggests that the concept of the "pure obsessional" (e.g., patients with unacceptable/taboo thoughts yet no compulsions) may be a misnomer, as these obsessions were factorially associated with mental compulsions and reassurance-seeking in these samples. These findings may have implications for DSM-5 diagnostic criteria., (© 2011 Wiley-Liss, Inc.)

Aims: This study investigated clinical and genetic predictors of increasing suicidal ideation during antidepressant treatment., Materials & Methods: A total of 131 depressed outpatients were allocated to four antidepressants (paroxetine, venlafaxine, clomipramine or nefazodone) in a sequential step procedure until remission. Suicidality was assessed using the 10th item of the Montgomery-Asberg Depression Rating Scale (MADRS). A total of 11 candidate genes involved in different mechanisms of antidepressant action were selected for association with increasing suicidality., Results: Increasing suicidality correlated with depression severity and higher antidepressant blood levels. Risk of increasing suicidal ideation was higher in subjects taking antidepressants other than paroxetine (odds ratio: 1.11). The strongest genetic predictor was found to be rs1360780 within the FKBP5 gene (p = 2.9 × 10(-5)), followed by 2677G>T in the ABCB1 gene. The rs130058 SNP within the 5-HTR1B gene demonstrated a differential association with increasing suicidal ideation depending on antidepressant type., Conclusion: Increasing suicidal ideation might be an adverse effect of antidepressants. The involvement of FKBP5 indicates that dysregulation of the hypothalamic-pituitary-adrenal axis is involved in treatment increasing suicidal ideation.