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A subgroup of patients with Panic Disorder (PD) exhibits increased sensitivity to caffeine administration. However, the association between caffeine-induced panic attacks and post-caffeine hypothalamic pituitary adrenal (HPA)-axis activation in PD patients remains unclear. In a randomized, double-blind, cross-over experiment, 19 PD patients underwent a 400-mg caffeine-challenge and a placebo-challenge, both administered in the form of instant coffee. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol and dehydroepiandrosterone sulfate (DHEAS) were assessed at both baseline and post-challenge. No patient panicked after placebo-challenge, while nine patients (47.3%) panicked after caffeine-challenge. Placebo administration did not result in any significant change in hormones’ plasma levels. Overall, sample’s patients demonstrated significant increases in ACTH, cortisol, and DHEAS plasma levels after caffeine administration. However, post-caffeine panickers and non-panickers did not differ with respect to the magnitude of the increases. Our results indicate that in PD patients, caffeine-induced panic attacks are not specifically associated with HPA-axis activation, as this is reflected in post-caffeine increases in ACTH, cortisol and DHEAS plasma levels, suggesting that caffeine-induced panic attacks in PD patients are not specifically mediated by the biological processes underlying fear or stress. More generally, our results add to the evidence that HPA-axis activation is not a specific characteristic of panic. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Objectives This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. Methods Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). Results Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. Conclusions Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

Background: The frequent occurrence of obsessive compulsive symptoms (OCS) in the course of schizophrenia and their impact on the functional outcome of the illness underlie the suggestion that the presence of OCS represents a separate subtype of schizophrenia, with a distinct clinical presentation and prognosis and specific neurobiological characteristics. This study investigated whether the presence of OCS in schizophrenia is associated with worse cognitive functioning in the domains of processing speed, executive functions and visuospatial memory. We also explored whether the degree of impairment in any of these cognitive domains could predict group membership (i.e. Schizophrenia with OCS [Sch-OCS] and Schizophrenia without OCS) and if there was a relationship between cognitive functioning and severity of OCS within the Sch-OCS group. Methods: Forty patients with schizophrenia, 20 with and 20 without OCS, individually matched for age, gender, years of education and severity of psychotic symptoms and 20 healthy controls underwent a comprehensive neuropsychological assessment. Results: Only lower performance in processing speed discriminated patients with OCS from patients without OCS. Processing speed impairment not only classified patients in OCS or non-OCS group but was also independent of the severity of OCS symptoms. Conclusions: The notion of additive effects of both schizophrenia and OCD on the structural and functional integrity of the brain circuits that support cognitive functions warrants further investigation in longitudinal neuropsychological and neuroimaging studies with larger samples and sufficient variation in the severity of OCS. (C) 2014 Elsevier Inc. All rights reserved.

Objectives. Major Depression with severe anxiety has been proposed as a distinct clinical variant of Major Depressive Disorder (MDD). This proposal invites the investigation of the differential biological correlates of the anxious versus non-anxious MDD. One such research area might be their possible differential associations with androgens. Methods. Plasma total testosterone and dehydroepiandrosterone were assessed in adequately matched female inpatients with anxious MDD, non-anxious MDD and normal controls. Results. Androgen levels were significantly lower in both patient groups compared to those of controls. Moreover, they were significantly lower in anxious MDD patients compared to those of their non-anxious MDD counterparts. The limitations of this study were cross-sectional design of the study, the small sample size of the study sample and the outpatient status of the control group. In addition, free testosterone levels were not measured. Conclusions. Our findings indicate that female major depression is associated with lower androgen levels, a deficiency aggravated by the severity of their concomitant anxiety.

ObjectiveLong-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. MethodsFourteen patients with long-term BDZ use (mean duration >15years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients’ CANTAB percentile score distributions were compared with normative CANTAB data. ResultsPatients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients’ scores on most tests remained still at the lower percentiles of CANTAB normative scores. ConclusionsAlthough preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up. Copyright (c) 2014 John Wiley & Sons, Ltd.

Objective. Anxious major depressive disorder (A-MDD) is differentially diagnosed from nonanxious MDD (NA-MDD) as MDD with a cut-off score >= 7 on the HAM-D anxiety-somatization factor (ASF). We investigated whether additional HAM-D items discriminate A-MDD from NA-MDD. Moreover, we tested the validity of ASF criterion against HAM-A, gold standard of anxiety severity assessment. Methods. 164 consecutive female middle-aged inpatients, diagnosed as A-MDD (n = 92) or NA-MDD (n = 72) by the normative HAM-A score for moderate-to-severe anxiety (>= 25), were compared regarding 17-item HAM-D scores. The validity of ASF >= 7 criterion was assessed by receiver-operating characteristics (ROC) analysis. Results. We found medium and large effect size differences between A-MDD and NA-MDD patients in only four out of the six ASF items, as well as in three further HAM-D items, namely, those of agitation, middle insomnia, and delayed insomnia. Furthermore, the ASF cut-off score >= 9 provided the optimal trade-off between sensitivity and specificity for the differential diagnosis between A-MDD and NA-MDD. Conclusion. Additional HAM-D items, beyond those of ASF, discriminate A-MDD from NA-MDD. The ASF >= 7 criterion inflates false positives. A cut-off point >= 9 provides the best trade-off between sensitivity and specificity of the ASF criterion, at least in female middle-aged inpatients.

Despite the general agreement that insight is a multidimensional phenomenon, the studies on the factorial structure of the scales for its assessment have yielded rather inconsistent results. The present study aimed to assess the internal structure of the Schedule for the Assessment of Insight (SAI-E). Seventy-two chronic patients with schizophrenia were assessed with SAI-E. Hierarchical cluster analysis and multidimensional scaling (MDS) were used to identify insight components and assess their inter-relationships. The associations of the extracted components with demographic, clinical and cognitive characteristics were also examined. The SAI-E demonstrated good psychometric properties. Three subscales of SAI-E were identified measuring awareness of illness, relabeling of symptoms, and treatment compliance. Moreover, the MDS disclosed two underlying dimensions - degree of ‘specificity’ and ‘spontaneity’ - within the insight construct. Treatment compliance was more strongly correlated with symptom relabeling than illness awareness. Excitement symptoms, global functioning and general intelligence were correlated with all the components of insight. Depressive symptoms were more strongly correlated with illness awareness. Impaired relabeling ability was linked to cognitive rigidity and greater severity of disorganization and positive symptoms. Education and severity of negative symptoms specifically affect treatment compliance. Our results support the hypothesis that insight is a multidimensional construct. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Preoccupation with body shape and weight is characteristic of both anorexia nervosa and bulimia nervosa. Despite their diagnostic and clinical significance, evidence on the nature of the underlying beliefs is relatively scarce. We used the Brown Assessment of Beliefs Scale (BABS) to assess the degree of delusionality of body image beliefs in seventy-two participants: 39 with anorexia and 33 with bulimia nervosa. We also investigated the relationship between body image delusionality and other clinical characteristics in eating disorders. Only patients with anorexia nervosa (28.8%) had delusional body image beliefs, whereas overvalued ideas appeared to be frequent in both anorexia and bulimia nervosa. Body image delusionality in anorexia nervosa was associated with restrictive eating pathology, early onset of the disorder and body dissatisfaction, whereas in the bulimia group it was linked to shorter duration of the illness, more intense dieting behaviors and specific psychological factors: ineffectiveness and maturity fears. Results suggest that a delusional variant of anorexia nervosa represents the one end of a continuum of insight among patients with eating disorders. Categorization of patients with eating disorders based on the level of delusionality of body image beliefs could facilitate further research on the role of insight deficits in these disorders. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

The therapeutic limitations of mainstay psychopharmacological treatments of obsessive-compulsive disorder (OCD) warrant the clinical testing of further add-on agents to improve patients’ clinical symptoms. One such agent might be pregabalin, which has been found efficacious in other anxiety disorders. We report on the findings of a small, 8-week open-label trial of adjunctive pregabalin with a 4-week follow-up in 10 OCD patients resistant or only partial responders to a combination of serotonin reuptake inhibitors with atypical antipsychotics. Adjunctive pregabalin at 225-675 mg/d was well tolerated and led to patients’ substantial improvement in their OCD symptoms, as reflected in their scores on the Yale-Brown Obsessive Compulsive Scale. Despite the several limitations of the study, its results suggest that adjunctive pregabalin might be a safe and efficacious new augmentation agent in the treatment of drug-resistant OCD. We hypothesize that pregabalin’s mechanism of action in OCD might consist in its inhibition of glutamatergic neurotransmission. Int Clin Psychopharmacol 26:221-224 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Both old and newer antidepressants and some atypical antipsychotics, such as ziprasidone and quetiapine, used as augmentation agents in severe major depression, are known to increase corrected QT (QTc) interval. We investigated the safety of the coadministration of electroconvulsive therapy with an antidepressant-ziprasidone-quetiapine combination with respect to QTc interval in 6 female patients with severe major depression resistant to pharmacotherapy alone. Each patient underwent a series of 10 to 11 sessions of bilateral electroconvulsive therapy. Corrected QT intervals were calculated at baseline and several times up to 10 minutes after seizure cessation. Overall, QTc interval changes remained within normal limits, without the occurrence of any cardiac adverse events. Our findings suggest that the coadministration of these treatments might be safe, at least with respect to QTc interval changes.

Several recent reports attest to zolpidem’s strong potential for abuse, dependence, and severe withdrawal symptoms upon its discontinuation. We report, for the first time, on 1 case of heavy zolpidem abuse and dependence with severe withdrawal symptoms twice treated safely and successfully with pregabalin, a newer antiepileptic agent devoid of known strong potential for abuse and dependence.

In clinical practice, a nonnegligible proportion of patients with mood or psychotic disorders undergo electroconvulsive therapy (ECT) concomitantly with pharmacotherapy. Ziprasidone, a combined serotonin and dopamine receptor antagonist, is a second-generation antipsychotic agent with a lower incidence of extrapyramidal motor symptoms and prolactin elevation and a safer profile of adverse effects on plasma lipids, glucose levels, and body weight than other anti-psychotics. To the best of our knowledge, there are as yet no available reports on the safety of the ECT-ziprasidone combination. We report here on a series of 8 female inpatients who underwent ECT while receiving ziprasidone (20-80 mg/d) as part of their regimen. Seven patients were treated for major depressive episode in the context of unipolar major depressive disorder (n = 5) or of bipolar disorder I (n = 2), whereas 1 patient was treated for exacerbation of schizophrenic symptoms. In all cases, the combination was well tolerated with only minimal adverse effects and unremarkable changes in corrected QT interval.

Background: Increased arterial stiffness (AS) might be one significant acute mediator of the well-attested association between female depression and cardiovascular disease. Methods: We tested this hypothesis in an inpatient sample of 20 drug-free women undergoing a new clinically severe major depressive episode of recent onset with an adequately matched mentally healthy control group. Patients’ clinical (Hamilton Depression Rating Scale) and vascular (Pulse-Wave-Velocity, PWV) assessments were performed both before the initiation and after the completion of their six-week antidepressant treatment. Results: Although initially patients exhibited significantly higher PWV values than controls, this was decreased and reached comparable levels to controls after treatment completion. Moreover, full-responders exhibited significantly greater vascular improvement than their partial-responders counterparts and the magnitude of their amelioration was strongly associated with the magnitude of their clinical improvement. Limitations: Our sample-size was small and patients’ follow-up short. Conclusions: Our findings provide support to the hypothesis that current severe major depressive episode in women leads acutely to aggravation of arterial stiffness, reversible however upon timely and effective antidepressant treatment. (C) 2009 Elsevier B.V. All rights reserved.

We review all available studies on the use of the newer anticonvulsant drug pregabalin (PGB) in the treatment of both alcohol dependence (AD) and benzodiazepine dependence (BD). In AD, the available evidence includes one open-label and one double-blind randomized studies, whereas in BD, only a few case reports and one open-label study are as yet available. In both conditions, PGB was found efficacious with significant improvement in withdrawal symptoms at the dosage ranges of 150-450 mg/day (AD) and 225-900 mg/day (BD). Moreover, its side effects were mild and transient. Despite the limited quality of the studies design, their findings suggest that PGB might constitute a novel efficacious and safe option in the treatment of both AD and BD.

Several anticonvulsants, although as yet not lamotrigine (LTG), have been found useful in the treatment of panic disorder with (PDA) or without agoraphobia. We administered LTG (200 mg/d) to 4 outpatients with PDA, as an augmentation therapy (3 patients with chronic and severe agoraphobia) or monotherapy (1 drug-naive patient with first-onset PDA) in a 14-week trial. The patient under LTG monotherapy improved significantly, whereas PDA symptoms in 2 of the other patients improved to some extent.

Despite the recent progress in the pharmacological treatment of obsessive-compulsive disorder (OCD) - especially with high doses of serotonin reuptake inhibitors, alone or in combination with low doses of antipsychotics - a non-negligible proportion of patients remains refractory to it. For these patients augmentation tactics with drugs from other chemical classes, including antiepileptic drugs, seems advisable. We report on the case of a female inpatient with OCD, whereby the adjunction of tiagabine, a selective GABA reuptake inhibitor at 15 mg/day, to a fluvoxamine (400 mg/day) - risperidone (1 mg/day) combination led to the patient’s marked improvement as reflected in the reduction by almost 47% of her score on the Yale-Brown Obsessive Compulsive Scale. With respect to tiagabine’s specifically anti-OCD mechanism of action, we note that enhanced inhibitory GABAergic neurotransmission slows down excitatory glutamatergic transmission in the cortico-striato-thalamic system, which presumably constitutes the core pathophysiological mechanism of OCD symptoms.

Extant pharmacological options for motor conversion disorder include mainly antidepressants and benzodiazepines. We report on the case of a 42-year-old female patient with frequent daily episodes of almost complete paralysis for the last 6 months resistant to an escitalopram-lorazepam combination at adequate doses. By contrast, the adjunctive administration of low-dose amisulpride at 200 mg/d to the patient’s regimen resulted in her substantial and durable improvement. We hypothesize that low-dose amisulpride, acting as a selective antagonist of D-2 and D-3 dopamine autoreceptors, might reverse the decreased activity of frontal and subcortical dopaminergic circuits presumably involved in motor control during hysterical paralysis.

Escitalopram (ESC) is the S-isomer of the racemic compound citalopram, and has been shown to be an efficacious treatment for major depressive disorder. Several studies or case reports are available describing its side effects, none of which however refer to its potential to induce ankle oedema. We report the case of a 69-year-old female depressed patient who, after approximately 1 month of therapy with ESC, progressively titrated up to 30 mg/day, developed a bilateral ankle oedema, which resolved completely within the first week following its discontinuation.

Objective: Breath-holding (BH) has been used as a simple probe to increase endogenous carbon dioxide (CO2). In patients with Panic Disorder (PD), lower baseline BH duration is associated with caffeine-induced panic attacks. In this paper, we assessed BH duration in PD patients in relation to panic attacks induced by caffeine intake. Methods: BH duration and state anxiety were assessed in 40 PD patients (12 males), both at baseline and after a 400-mg caffeine challenge test. Results: Patients panicking after caffeine administration (14 patients, 4 males) exhibited a significant reduction of their post-challenge BH duration, while no change of the BH duration was observed in non-panicking patients (26 patients, 8 males), Reduction in post-challenge BH duration was not related to higher anxiety levels - as reflected in the State-Trait Anxiety Inventory-State Form scores - independently of the occurrence of a panic attack. Panickers exhibited significantly lower baseline BH duration, compared to non-panickers. Conclusions: Our findings indicate that in PD patients, caffeine-induced panic attacks are strongly associated with a significant reduction of BH duration at both pre- and post-challenge. jointly, these findings suggest that in a Subgroup of PD patients, sensitivity to endogenous CO2 accumulation may underlie both the lower BH durations and the caffeine-induced panic attacks. In this subgroup of PD patients, caffeine might exert its panicogenic properties through the exacerbation of patients’ already pathological hypersensitivity to CO2 accumulation, as indicated by both the significant decrease of their BH duration at post-challenge and by their significantly lower baseline BH duration respectively. (c) 2008 Elsevier Inc. All rights reserved.

Tolerance, dependence, and adverse effects on cognitive functions are well known consequences of long-term use of benzodiazepines (BDZ), especially at high doses; this raises thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer antiepileptic, pregabalin (PGB), which has already successfully been tested in the treatment of anxiety disorders. We report on a series of four women with long-term, high-dose dependence on BDZ, who were treated with PGB at doses of 225-600 mg. All four patients discontinued BDZ successfully in 3-7 weeks. Moreover, they had an impressive reduction of their previous anxiety levels under BDZ. In addition, the patients showed a clinically significant amelioration in their cognitive functioning. The side effects of PGB were mild and transient, persisting only during the first 2 weeks of treatment. Although our findings are preliminary, they suggest that PGB might be one of the most promising of the newer agents in the treatment of BDZ dependence.

In clinical practice, a proportion of patients with psychotic or mood disorders are treated with electroconvulsive therapy (ECT) while receiving concomitantly antipsychotic and/or other psychotropic agents. Aripiprazole is a second-generation antipsychotic that seems to have a favorable side-effect profile. However, to the best of our knowledge, there are, as yet, no available reports oil the safety of ECT-aripiprazole combination. We report the cases of 4 female inpatients-3 suffering from major depression and I from schizophrenia-who underwent ECT-1 of them twice-while receiving aripiprazole (10-15 mg/d), as part of their regimen. I it all cases, the combination was well tolerated and only minimal side effects were reported.

Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 g/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect.

Objective Tolerance, dependence, and adverse effects on cognitive functions are well-known consequences of long-term use of benzodiazepines (BDZ), especially at high doses, raising thorny therapeutic problems in their discontinuation. One promising pharmacological agent in BDZ discontinuation might be the newer anti-epileptic pregabalin, already successfully tested in the treatment of anxiety disorders. Methods We report on a sample of 15 patients with long-term, mostly high-dose dependence from BDZ, treated with pregabalin in an open-label study at doses 225-900 mg. Results All patients discontinued successfully BDZ in 3-14 weeks, moreover with a significant reduction of their previous anxiety levels under BDZ. In addition, patients showed also a significant amelioration in their cognitive functioning. Pregabalin’s side-effects were mild and transient, lasting only during the first 2 weeks of treatment. Conclusion Although preliminary, our findings suggest that pregabalin may be one new promising agent in the treatment of BDZ dependence. Copyright (c) 2008 John Wiley & Sons, Ltd.

Antiepileptic drugs (AED) are increasingly used in the treatment of migraine. Pregabalin (PGB) is an AED that has been used in the treatment of partial seizures, of various types of pain, and of certain anxiety disorders, but to the best of our knowledge, there has been no report on the use of PGB in the treatment of migraine. We report the case of a 60-year-old female inpatient with depression, long experiencing migraine, whose migraine symptoms improved markedly after receiving PGB in combination with escitalopram administered for her depression. The PGB mechanism of action in conjunction with its structural similarity with gabapentin, already successfully tested in the treatment of migraine, provide additional supportive evidence, theoretical and clinical, respectively, for PGB potential to alleviate migraine symptoms. However, only carefully randomized, controlled studies, or at the very least, open-label series of large patient samples treated in a similar fashion could establish the efficacy of PGB in migraine treatment.

It has been suggested that the efficacy of electroconvulsive therapy (ECT) in the treatment of major depressive episodes may be enhanced by concurrent administration of antidepressant medication. Therefore, the issue of how safe the combination of these 2 treatment modalities is warrants investigation. Escitalopram (ESC) is a novel selective serotonin reuptake inhibitor that seems to have a favorable side effect profile. To the best of our knowledge, there is no report on the safety of the ECT-ESC combination. We report the cases of 3 female inpatients with major depressive episode-two in the context of major depressive disorder and one in the context of bipolar disorder I-who underwent ECT while Concurrently receiving ESC (20 mg/d) as part of their regimen. In all cases, the combination was well tolerated, and only minimal side effects were reported.