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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.)

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.

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.

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.)

Compulsive skin picking, 'acne excoriee', neurotic (psychogenic) excoriation, dermatotillomania, occurring in 2% dermatology patients mostly in women, is a result of excessive scratching, picking, gouging or squeezing of the skin using teeth, tweezers, nail files, pins and knives, etc. The lesions are usually found on face and also on upper limbs and upper back, areas patients can easily reach. They may occur in absence or in response to skin pathology or sensation of itching. A young female patient attended OPD with the complaints of multiple excoriated lesions over the face, arms and forearms. The diagnosis was psychogenic excoriation which is an uncommon psychodermatological condition. She was treated with fluoxetine and behaviour therapy. The patient recovered fully with above treatment at the end of 3 months. Psychogenic excoriation is an uncommon psychodermatological condition which responds well to selective serotonin reuptake inhibitors and behaviour therapy (habit reversal training).

Objective: To assess the clinical and polysomnographic features of narcolepsy in Saudis., Methods: All patients diagnosed to have narcolepsy in the Sleep Disorders Center at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between March 1998 and December 2005 based on the International Classifications of Sleep Disorders Diagnostic and Coding Manual criteria were included. A data entry form collecting the demographic, clinical features, medications, referring specialty, prior diagnoses and daytime sleepiness was used. All patients underwent polysomnography followed by multiple sleep latency., Results: Forty-seven patients with a mean age of 28.9 +/- 1.9 years were included. The mean age at onset of symptoms was 20.5 +/- 1.4 years. The interval between symptoms onset and diagnosis was 8.4 +/- 1.2 years. While 22 (46.8%) of the patients were referred to the sleep disorders clinic by different specialties, 25 (53.2%) patients sought an appointment in the sleep disorders clinic directly. Only 3 patients were referred with the correct diagnosis. Nocturnal sleep quality was worse in narcoleptics with cataplexy compared to those without cataplexy., Conclusion: Saudi patients with narcolepsy have the same clinical presentation as reported in the Western literature. Narcoleptics with cataplexy had disturbed quality compared to narcoleptics without cataplexy. A long time was reported between symptoms onset and diagnosis, which may reflect the under-recognition of the problem among physicians.

Premature ejaculation is a common symptom that can provoke relapse in formerly opioid-dependent men after detoxification. The purpose of this study was to compare the efficacy of clomipramine and fluoxetine for the treatment of premature ejaculation in formerly opioid-dependent men after detoxification. Sixty opium-detoxified men with A & B DSM-IV diagnostic criteria for premature ejaculation participated in a prospective two-week descriptive inferential clinical trial after a two-week washout period. The subjects did not consume any other medications but naltrexone for maintenance of an opium-free state. The subjects were randomly divided into two groups of thirty subjects, one group received fluoxetine (10 mg/d for the first and 20 mg/d for the second week), and the other received clomipramine (25 mg/d for the first and 50 mg/d for the second week). Twenty five subjects did not continue the treatment and were lost to follow-up. The severity of the premature ejaculation was graded regarding the subjects' report in weeks 0, 1, and 2. Mann Whitney-U and Wilcoxon non-parametric tests were used for statistical analysis. Fluoxetine (10 mg/d then 20 mg/d) and clomipramine (25 mg/d then 50 mg/d) were both effective in the treatment of premature ejaculation and did not show any difference in efficacy. The severity of premature ejaculation did not show any relation to the subjects' age, education level, opioid type, or route of abuse. Fluoxetine and clomipramine both can be equally used in the treatment of premature ejaculation following opioid detoxification, depending on their side effects and other symptoms in the subjects.

Objectives: To determine whether clomipramine differs from fluoxetine in reducing feline urine marking; whether reduction of marking continues in cats treated >8 weeks; whether recurrence of marking, after abrupt drug withdrawal, is less in cats treated >8 weeks; and whether cats that are successfully treated but resume marking after drug withdrawal can be successfully treated again with the same drug regimen., Design: Positive-controlled, double-masked clinical trial., Animals: 22 neutered cats (2 females, 20 males) > or =1 year old with objectionable urine marking., Procedure: Cats that marked vertically > or =3 times/wk were treated with fluoxetine (1 mg/kg [0.45 mg/lb], q 24 h, PO) or clomipramine (0.5 mg/kg [0.23 mg/lb], q 24 h, PO) for 16 weeks, and efficacy was compared. Recurrence of marking was determined after abrupt withdrawal of fluoxetine at 16 or 32 weeks. Reduction in marking in cats treated with fluoxetine for 8 weeks after returning to marking following drug withdrawal was compared with the initial 8 weeks of successful treatment., Results: Efficacy of fluoxetine and clomipramine was similar. Treatment >8 weeks revealed increasing efficacy in reduction of marking. Return of marking after termination of fluoxetine administration occurred in most cats. Cats successfully treated initially with fluoxetine responded similarly to repeated treatment., Conclusions and Clinical Relevance: Clomipramine and fluoxetine were equivalent in treating urine marking. Longer treatment increased efficacy. Most cats return to marking after abrupt drug withdrawal. A second course of treatment can be expected to be as effective as the first.

The aim of this study was to evaluate the effectiveness of the addition of manual-based cognitive-behavioral therapy to a medication regimen of clomipramine and fluoxetine and the withdrawal of medication during cognitive-behavioral therapy. The participant was an 11-year-old girl with symptoms of obsessive thoughts about germs and illness and handwashing compulsions. The addition of cognitive-behavioral therapy reduced the participant's daily number of obsessions and avoidance behaviors after three sessions. When medication was tapered during the cognitive-behavioral therapy program, the participant's symptoms continued to decline, and after treatment, she no longer met diagnostic criteria for obsessive-compulsive disorder. Impressively, the participant remained medication free and treatment gains were maintained at 4 months' follow-up.

Cytochrome P450-2D6 may be involved in the metabolism of many drugs such as psychotropic drugs and its genetic polymorphism is responsible for inter-individual differences in the therapeutic effect and toxicity of these drugs. Moreover with the same genetic basis, CYP2D6 metabolic capacity variations are observed. Different factors of variation may be involved, among them the prescribed drugs. The aim of this study was to compare the influence of two types of antidepressants, tricyclic (clomipramine) and serotonergic specific recapture inhibitor (SSRI) (fluoxetine), on the CYP2D6 metabolic capacity of depressed inpatients. The CYP2D6 phenotype (dextromethorphan test) was determined in 56 genotyped (PCR-SSCP) depressed caucasian inpatients with a heterozygous genotype. Forty-five subjects were treated with clomipramine and eleven received fluoxetine. The dextromethorphan metabolic ratio (MR) median was significantly higher in the fluoxetine group (0.255) than in the clomipramine group (0.083, p < 0.014). In this study, fluoxetine involved a greater decrease of CYP2D6 metabolic capacity than clomipramine. Clinical implications and the possible connection between a decreased CYP2D6 activity and adverse drug effects were discussed. Caution should be taken when drugs with a low therapeutic index must be coprescribed in such patients., (Copyright 2004 John Wiley & Sons, Ltd.)

Background: Multiple lines of evidence suggest continuity from adolescent to adult depression, but treatment response is different in the two groups. There is some consensus that noradrenergic drugs are ineffective in adolescent depression. The aim of this study was to see whether this poor response extended to young adults., Methods: Patients from two randomised studies on prediction of antidepressant response were used. The subjects were divided into a youth sample (ages 18-24) and an older sample (ages 25 and over). The 6-week percentage response, based on HDRS scores, and the number of patients in remission (i.e., HDRS < or =7) at 6 weeks were compared in subjects who received a serotonergic (clomipramine (mean dose 145 mg) and fluoxetine (mean dose 27 mg)) or a noradrenergic (desipramine (mean dose 200 mg) and nortriptyline (mean dose 100 mg)) antidepressant., Results: There were no significant differences between the two studies, except for a small variation in baseline Hamilton scores. Young adults had a poorer response to noradrenergic antidepressants than they did to serotonergic antidepressants, whereas there was no differential response in the older age group. Young adults had a lower rate of remission on a noradrenergic antidepressant (38% noradrenergic versus 72% serotonergic) but there was no significant difference in remission rates in older adults (65% noradrenergic versus 57% serotonergic) or the sample as a whole (54% noradrenergic versus 62% serotonergic)., Limitations: The age cut-off at 24 is somewhat arbitrary. One study was double-blind while the other was open. There was no placebo control., Discussion: While the response rate to noradrenergic antidepressants in young adults is lower, it is not clear whether this is comparable to adolescents. The reasons for a reduced response may be related to maturation of the noradrenergic system in the brain. Our results suggest that age may be one factor to consider when choosing antidepressants for patients.

Serotonin re-uptake inhibitors (SRIs), clomipramine and selective serotonin re-uptake inhibitors (SSRIs), are the first-line pharmacologic therapies for patients with obsessive compulsive disorder (OCD). However, 40 to 60 per cent of patients do not respond to adequate treatment trials of SRIs. SRI partial- and non-responders must be treated with augmentation strategies or put on another SRI since non-response to the first SRI does not necessarily indicate a non-response to a second SRI. Each treatment trial should run at least 10 weeks and if successful, the drug should be continued for at least 1 to 2 years and withdrawn gradually. The presented patient had a second episode of OCD which was resistant to more than 10 weeks of high dosage clomipramine even though he responded very well during the first episode 4 years earlier and had been off clomipramine for 3 years. Augmentation to clomipramine with lithium and then haloperidol consecutively also failed. When clomipramine was changed to fluoxetine, the OCD symptoms were responsive even at a starting dosage of 20 mg/day. The response improved as the dosage of fluoxetine was increased. The response reached a maximum and the patient coped very well in every aspect of daily life when the dosage of fluoxetine was increased to 60 mg/day. He had taken fluoxetine at this daily dosage for one year before the drug was tapered off. It has now been more than two years since he has had any OCD symptoms and clomipramine was terminated.

In the phase III of the french national study on OCD, 155 patients suffering from an OCD (full DSM III-R criteria, score on NIMH-OC > or = 7, not treated or undertreated) had entered a naturalistic follow-up of 12 months duration. Obsessions, compulsions, depression, anxiety, impulsivity and global functioning were assessed by using NIMH-OC, CPRS-OC2, MOCI, MADRS, HAD (-A, -D), BDS (Behavioral Dyscontrol Scale), CGI and GAS (DSM III-R). From the initial population (155 patients), 130 (84%) had been treated with drugs and were "completers" and assessed at M6 and M12; 18 (11.6%) were lost to follow-up and 7 (4.5%) had dropped out because of treatment refusal, side-effect or improvement. Only 19% of patients had received a behavior therapy. In spite of selection of patients with severe and chronic OCD associated to depression (mean MADRS score = 25), 85% of treated patients had been treated with one anti-OCD drug (105 with fluoxetine, 17 with clomipramine and 17 with other antidepressants), 4.5% needed a treatment substitution and 4.5% a bitherapy (combination of 2 anti-OCD drugs); 84% of patients were considered as "good compliant" with visit agenda and treatment. At the end of follow-up, global improvement was observed in 77% of patients treated. Clinical improvement was assessed by different response criteria (final NIMH-OC score, 30% decrease on NIMH-OC, 35% decrease on MOCI, final GAF score > or = 70) which showed 4 patterns of response to treatment: "positive response on M6 and M12" = 43-64%; "only M12" (slow response) = 13-24%; "only M6" (escape or relapse) = 4-6%; "negative response on M6 and M12" (resistant OCD) = 19-33%. During 12 month treatment, 31 patients (22.5%) had presented an adverse effect in which 7 cases (5.1%) with "serious adverse event" and 5 cases (3.6%) who required treatment drop-out. Predictive factors of clinical response to anti-OCD drugs were explored: 1) "lack of insight" was the best factor to characterise the resistant group; 2) high base-line of "impulsivity" predict better response at M6; 3) important to severe slowness was associated with a longer delay to response (between M6 and M12). The results of the phase III from the french multi-site study will be compared to the international data on long-term treatment of OCD.

Objective: To examine the efficacy and tolerability of clomipramine compared with the selective serotonin reuptake inhibitors (SSRIs) in the treatment of obsessive-compulsive disorder (OCD), bearing in mind the recent Expert Consensus Guidelines recommendation to use clomipramine after 2 to 3 failed SSRI trials., Method: The literature on the pharmacotherapy of OCD was critically examined., Results: The available research evidence is not conclusive but suggests that clomipramine possesses greater anti-obsessional efficacy than do the SSRIs. In addition, when clomipramine is presented to patients in a positive way, and properly used in small initial doses with gradual increases, it seems to be tolerated as well as the SSRIs., Conclusion: Recently expressed opinions that clomipramine should be used to treat OCD after 2 to 3 failed SSRI trials are not supported by research evidence. Both clomipramine and the SSRIs may be used as first-line treatments for OCD.

This article reviews the advances in pharmacotherapy of paraphilias. Antiandrogen hormones, phenothiazines, and lithium therapy of paraphilias is briefly reviewed. Pharmacotherapy of paraphilias with serotonergic drugs such as fluoxetine, clomipramine, sertraline, and fluvoxamine is reviewed in detail. In addition, the use of buspirone hydrochloride in paraphilias is discussed. The final focus of the article is on the etiologic theories of paraphilias and some practical advice for the pharmacotherapy and management of paraphilias.

Purpose: We compared the efficacy and safety of fluoxetine, sertraline, clomipramine and placebo for the oral pharmacotherapy of premature ejaculation., Materials and Methods: The study included 36 men (mean age 44 years) who had intravaginal ejaculation latency of less than 2 minutes. Patients took each of 3 drugs and the placebo consecutively during a 4-week period per each agent. Efficacy and side effects data were obtained by a self-reported patient questionnaire that rated intravaginal ejaculation latency, sexual satisfaction of patient and partner, and possible side effects., Results: After 4 weeks of treatment with placebo, fluoxetine, sertraline and clomipramine the mean intravaginal ejaculation latency time was significantly increased from 46 seconds to 2.27 minutes, 2.30 minutes, 4.27 minutes and 5.75 minutes, respectively (all p <0.01). However, treatment with clomipramine or sertraline caused a greater increase in mean intravaginal ejaculation latency time than fluoxetine or placebo (p <0.01). Patient sexual satisfaction rate after treatment with clomipramine was significantly higher (p <0.05) than with sertraline, fluoxetine or placebo. Partner sexual satisfaction rate was also higher with clomipramine than with sertraline or fluoxetine but no statistical difference was found. The incidence of side effects with clomipramine was significantly higher (p <0.05) compared to that of fluoxetine, sertraline and placebo, while no significant difference among sertraline, fluoxetine and placebo was noted., Conclusions: In men with premature ejaculation clomipramine was the most useful drug in terms of efficacy. Treatment with sertraline was nearly as effective and had a lower incidence of side effects.

Unlabelled: Serotonin syndrome is the result of the drug interaction that enhances serotonergic tone in the central nervous system. The neurological manifestations are transient in most of the reported cases with rare fatality., Case Description: A 30-year-old woman developed ischemic infarction of the right temporoparietal and cerebellar hemispheres 48 hours after administration of a large dose of clomipramine. This drug was given within 24 hours of discontinuation of high-dose fluoxetine, both of which are known to enhance serotonergic tone in the central nervous system. The distribution of the ischemic infarction in this case did not respect the major territorial arteries and was similar to spreading oligemia/ischemia that is described in migraine. A similar pathogenesis may exist for stroke in serotonin syndrome and in migraine.

The SSRI antidepressants have emerged as effective new treatment for patients with premature ejaculation whether or not these patients suffer from depression. Clomipramine, fluoxetine, paroxetine, and sertraline seem to be a safe treatment option for patients with premature ejaculation, especially in cases of failed psychological treatment, in rejection of psychological treatment, and when partners are unwilling to cooperate in treatment. Further controlled and larger studies that focus on clinically relevant issues such as dose, length of treatment, maintenance of beneficial effects after treatment discontinuation, and the combination of pharmaco- and behavior therapy for premature ejaculation are warranted. Other medications, such as benzodiazepines, may be useful in some cases of premature ejaculation.

There is evidence of the clinical efficacy and safety of clomipramine and the newer selective serotonin reuptake inhibitors (SSRIs) for the treatment of obsessive-compulsive disorder (OCD). In the present study, we have compared the efficacy and safety of 40 mg/day of fluoxetine and 150 mg/day of clomipramine in patients with OCD, diagnosed according to DSM-IIIR. A total of 55 patients entered this 8-week, double-blind controlled study. Efficacy for both drugs was comparable. The primary efficacy criterion, the Y-BOCS Total score, did not show any significant differences between treatment arms. Response rate was higher with clomipramine, using a 25% decrease in Y-BOCS Total score as response threshold, but there were no significant differences between treatment arms using a 35% threshold. Overall safety and tolerability were good for both drugs, being slightly better for fluoxetine.

Quality of life is one of the effectiveness measures used to assess the impact of medical interventions. This paper describes results of a study on quality of life of depressed patients treated with fluoxetine or tricyclic antidepressants (TCAs) such as amitriptyline and clomipramine. The quality of life of patients was measured using the Short Form (SF-36), a widely accepted and validated questionnaire. Depressed patients (n = 845) were observed using a cross-sectional design. Patients who had been under treatment for at least 1 week (amitriptyline, clomipramine or fluoxetine) and met the DSM-III-R criteria for major depressive disorder were included. Similar sociodemographic profiles were found across treatment groups. However, more patients with a history of depression were found in the TCA vs the fluoxetine group. Compliance was dramatically lower and length of treatment higher for TCA-treated groups. Controlling for confounding variables, the TCA-treated group also scored lower than the fluoxetine-treated one for general health perception, and social and physical functioning. These differences are not explained by symptom severity since Hamilton scores were similar across treatment groups. These results suggest that fluoxetine treatment may be associated with higher levels of social functioning and health perception than usual TCA treatment.

Background: Although a large body of evidence indicates the efficacy of pharmacotherapy in the treatment of obsessive-compulsive disorder (OCD), a considerable percentage of these patients do not respond. Very few studies focus on factors related to treatment response of OCD. The purpose of this study was to investigate which clinical factors are related to drug treatment response in OCD., Method: We examined 53 OCD patients treated with either clomipramine or fluoxetine for a period of 6 months, dividing the sample into "responders" and "nonresponders" to treatment. At admission, patients were evaluated using a semistructured clinical interview, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the Hamilton Rating Scale for Depression, and the Hamilton Rating Scale for Anxiety. We then compared acute-phase patient characteristics and response to drug treatment. Response was defined as a decrease of at least 40% in the Y-BOCS total score and a rating of "improved" or "very improved" on the Clinical Global Impressions scale within 16 weeks of treatment and maintained over three consecutive evaluations., Results: By the sixth month of treatment, 31 patients (58.5%) responded to either clomipramine or fluoxetine. Nonresponders had lower age at onset and longer duration of the disorder; in addition, they showed higher frequency of compulsions, washing rituals, chronic course, concomitant schizotypal personality disorder, and previous hospitalizations. A worse response to drug treatment was predicted in a stepwise multiple regression by (1) concomitant schizotypal personality disorder, (2) presence of compulsions, and (3) longer illness length., Conclusion: Our findings suggest that there are distinct types of OCD with respect to drug treatment response. They provide indirect evidence of treatment specificity by identifying characteristics responsive to different modalities, which may be of value in the selection of patients for alternative treatments.

The selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor fluoxetine is an effective antidepressant in elderly patients. Its efficacy is similar to that of other frequently used antidepressants, such as the tricyclic antidepressants. However, compared with the tricyclic antidepressants, fluoxetine has a more favourable tolerability profile and is less toxic in overdose. It is associated with fewer anticholinergic, cardiovascular and CNS adverse events, but greater numbers of gastrointestinal adverse events than have been reported for the tricyclic antidepressants. This is important in elderly patients who are more at risk of developing central anticholinergic and cardiovascular effects than are younger patients. Therefore, while its position relative to other selective serotonin reuptake inhibitors requires investigation, fluoxetine represents a major advance over tricyclic antidepressant agents in the treatment of elderly patients with depression, predominantly because of its favourable tolerability profile.

A preliminary trial with fluoxetine, a 5-HT reuptake inhibitor, was carried out on two young male patients (21 and 32 years old) affected by Gilles de la Tourette syndrome. They both underwent a complete neurological evaluation also including neuroradiological, neurophysiological and neuropsychological assessment. Both patients had already been treated with benzodiazepines and amitriptyline; the older one was also given haloperidol and chlorimipramine with definite, but short-lasting improvement. During hospitalization a therapeutic trial with fluoxetine (20 mg/day in the younger patient and 40 mg/day in the older) in association with chlorimipramine (75 mg/day) was initiated, leading to a significant reduction (at least 50%) of abnormal movements and obsessive-compulsive behaviour. The older patient had no side effects while the 21 year old subject complained of insomnia, urinary retention and anorexia; despite the objective improvement, these side effects led us to modify the therapy after the first month. The favourable action of serotoninergic agents on TS symptoms supports the hypothesis that the multiple tics of the syndrome are motor compulsions.

A multiple regression/discriminant analysis of positron emission tomographic cerebral metabolic (rCMRglc) data in 10 obsessive-compulsive disorder (OCD) patients before and during pharmacotherapy was carried out to see if rCMRglc interdependencies distinguished OCD patients from controls. Before therapy, a discriminant function reflecting parietal, sensorimotor, and midbrain rCMRglc interdependencies correctly classified eight (80%) of the 10 patients as OCD; after therapy, six (70%) were classified as controls, most of whom were responders. Before therapy, rCMRglc interdependencies involving basal ganglia, thalamus, limbic, and sensory and association cortical regions distinguished 67% of patients who clinically responded to drug (RESP, n = 6) and 75% of patients who did not (NRESP, n = 4) from controls. After therapy, all RESP were classified as controls; classification of NRESP remained unchanged. The results suggest the conjunctive utility of this method to assess individual differences in rCMRglc during pharmacotherapy, and to explore the neurobiology of OCD.

The most common effective treatments for obsessive-compulsive disorder include clomipramine, fluoxetine, and exposure-based behavior therapy. A meta-analysis was conducted on the results from 25 appropriate treatment studies (1975-1991). All three treatments were significantly effective for most of the outcome variables (overall severity, anxiety, depression). Exposure was not significantly effective for reducing depressed mood. More treatment outcome studies are needed before a clearly superior treatment or combination of treatments can be statistically determined.

Two patients suffering from severe obsessive-compulsive disorder which had proven refractory to clomipramine and/or phenelzine treatment were successfully treated with fluoxetine, a new drug with a strong serotonin uptake inhibiting action. Outcome of treatment was measured on psychometric tests including the Leyton Obsessive Inventory, Hopkins Symptom Checklist-90, Beck Depression Inventory, and daily self-reports of the duration and degree of discomfort of their most severe obsessions. The delay in responding to fluoxetine, the continuing improvement even after one year on the drug, and the prompt relapse with abrupt withdrawal of treatment were noted.

A sample of 120 patients, all of whom met DSM-III criteria for major unipolar depressive disorder, were randomly allocated to two treatment groups. Sixty patients were treated with fluoxetine and 60 with clomipramine during a 6-week period. No significant difference was found in antidepressant efficacy, with improvement occurring on both drugs. Important differences were found in the side-effects profile of each group, their incidence being significantly lower and tending to disappear during the course of treatment in the group of patients treated with fluoxetine.

8 general practitioners and 7 specialists in the field of psychiatry and neurology participated in this study evaluating the results of fluoxetine treatment in outpatients with depression in respect to safety and efficacy. They were familiarized with the requisite instruments by video rater training. The study was designed as a randomised double-blind parallel study involving 139 patients, comparing the effects of a daily dosage of 20 mg fluoxetine, 40 mg fluoxetine and 50 mg clomipramine. The number of patients treated in each group was 45, 46, and 48, respectively and altogether 125 completed the four-week study (five visits). A comparison of overall efficacy ratings showed significant antidepressant efficacy in all three treatment groups. On day 14 of the study (visit 4), patients receiving 40 mg fluoxetine showed significantly (p less than 0.05) better global improvement than patients receiving clomipramine. Treatment was well tolerated by all patients. The frequency of adverse events in response to fluoxetine was lower than under clomipramine treatment. On comparing treatment by psychiatrist and general practitioner no significant differences were found regarding age, sex, number of previous episodes and duration of the recent episode and outcome. Severe depression tended to be treated by psychiatrists; general practitioners prescribed additional medication less frequently.

Moral or religious scrupulosity is a disabling condition which is sometimes seen in patients with obsessive compulsive disorder (OCD). The authors described 10 patients with moral or religious scrupulosity who were treated with fluoxetine or clomipramine. Seven of the 10 patients completed open treatment of at least 8 weeks without requiring adjunctive medication; 5 of those 7 patients were rated as much improved. Among the 3 patients who required adjunctive medication, 1 was rated as much improved. Of the 4 nonresponders at 3 months, 2 responded after longer treatment trials. These results suggest that extreme moral or religious concerns and behaviors might be a form of OCD and that the scrupulosity can be effectively treated with serotonin reuptake blockers.

Treatment with fluoxetine hydrochloride was compared with treatment with clomipramine hydrochloride in two groups of patients with obsessive-compulsive disorder using two different experimental designs. In the first group of 11 patients with obsessive-compulsive disorder studied using a randomized, double-blind, crossover design, treatment with fluoxetine for 10 weeks was found to produce therapeutic effects similar to treatment with clomipramine for 10 weeks. There were significantly fewer total side effects reported during fluoxetine than clomipramine treatment. Drug tapering and placebo substitution in the 4-week crossover interval phase led to substantial relapses in obsessive-compulsive disorder symptoms and depression. Furthermore, responses to the second drug took as long to occur as responses to the first drug, although both drugs are thought to act by a common mechanism, serotonin uptake inhibition. A second group of 21 patients with obsessive-compulsive disorder that had been previously stabilized on clomipramine treatment with at least partial benefit were crossed over to fluoxetine treatment in a double-blind fashion. After 10 weeks of fluoxetine administration, most patients manifested behavioral rating scores of obsessive-compulsive disorder and depressive symptoms that were comparable with precrossover ratings completed during clomipramine treatment. A significant exacerbation in obsessive-compulsive disorder and depression ratings as well as a similar lag in therapeutic efficacy were also noted in this second cohort of patients with obsessive-compulsive disorder. Platelet 5-HT concentrations were reduced 95% during both clomipramine and fluoxetine treatment periods. These results suggest that fluoxetine may represent a viable alternative to clomipramine in the treatment of obsessive-compulsive disorder, although further studies with larger sample sizes are needed.

Since it will be some time until data will be available comparing clomipramine and fluoxetine for the treatment of patients with obsessive-compulsive disorder (OCD), a meta-analysis of previous studies was performed in an attempt to gain some information about comparable efficacy and side effects of these two commonly used agents. In 31 OCD patients receiving clomipramine in a controlled trial and 72 OCD patients receiving fluoxetine openly, both drugs appeared effective, with clomipramine having a somewhat larger effect than fluoxetine. Different side effect profiles may have a bearing on patient selection.

Clomipramine has been reported to be effective in the treatment of obsessive-compulsive disorder (OCD). Children and adolescents, however, tolerate poorly the adverse effects of tricyclics. Fluoxetine and other serotonin re-uptake inhibitors also appear useful in OCD, and are safer than clomipramine. To maximize the therapeutic effects and minimize adverse effects, 6 adolescents with OCD were treated in single trials with a clomipramine-fluoxetine combination. Duration of combined drug therapy ranged from 4 weeks to more than 28 weeks. Patients were first treated with clomipramine alone; if improvement or adverse effects were unsatisfactory, they received the drug combination. Clinical global improvement with clomipramine alone was moderate in 3 patients and minimal in 3. With a combined clomipramine-fluoxetine therapy, improvements were marked in 5 patients, and moderate in 1. These improvements were obtained with relatively low daily doses: clomipramine at 25 to 50 mg, and fluoxetine at 20 to 40 mg. Adverse effects appeared greater and much less tolerable with clomipramine alone than with the clomipramine-fluoxetine combination. This drug combination was well tolerated. These preliminary data suggest that relatively low doses of a clomipramine-fluoxetine combination may potentiate therapeutic effects and minimize adverse effects in OCD patients. Larger controlled trials are suggested.

The authors describe five patients with body-dysmorphic disorder who responded preferentially to serotonin reuptake blockers. They review the literature, describe how patients with excessive concern about body abnormalities lie along a spectrum of doubt and certainty, and discuss similarities and differences between this disorder and obsessive-compulsive disorder.