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Objectives: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear., Methods: We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less., Results: Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission., Conclusions: Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.

Purpose: Clozapine is an atypical neuroleptic agent, effective in treating drug-resistant schizophrenia. The aim of this work was to investigate overall sleep architecture and sleep spindle morphology characteristics, before and after combination treatment with clozapine, in patients with drug-resistant schizophrenia who underwent polysomnography., Methods: Standard polysomnographic techniques were used. To quantify the sleep spindle morphology, a modeling technique was used that quantifies time-varying patterns in both the spindle envelope and the intraspindle frequency., Results: After combination treatment with clozapine, the patients showed clinical improvement. In addition, their overall sleep architecture and, more importantly, parameters that quantify the time-varying sleep spindle morphology were affected. Specifically, the results showed increased stage 2 sleep, reduced slow-wave sleep, increased rapid eye movement sleep, increased total sleep time, decreased wake time after sleep onset, as well as effects on spindle amplitude and intraspindle frequency parameters. However, the above changes in overall sleep architecture were statistically nonsignificant trends., Conclusions: The findings concerning statistically significant effects on spindle amplitude and intraspindle frequency parameters may imply changes in cortical sleep EEG generation mechanisms, as well as changes in thalamic pacing mechanisms or in thalamo-cortical network dynamics involved in sleep EEG generation, as a result of combination treatment with clozapine., Significance: Sleep spindle parameters may serve as metrics for the eventual development of effective EEG biomarkers to investigate treatment effects and pathophysiological mechanisms in schizophrenia.

The antiepileptic agent topiramate has proved its efficacy in a variety of other conditions as well, including several kinds of tremor and migraine prophylaxis. We report on the case of a 42-year-old depressive female patient with comorbid migraine attacks, whereby the adjunction of topiramate as an antimigraine agent at the dosage of 50 mg/d to her antidepressive treatment with fluvoxamine at 300 mg/d triggered--the prima facie paradoxical for topiramate--side effects of tremor and myoclonus. Topiramate was immediately discontinued, and patient's abnormal movements subsided completely within 24 to 72 hours. Topiramate was possibly the cause of patient's abnormal movements enhanced by fluvoxamine's potential to induce also tremor and myoclonus. Therefore, clinicians should be aware of the potentially severe adverse reactions that might occur during concomitant treatment with fluvoxamine and topiramate.

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.

The possible association between phospholipase A2 gene and bipolar mood disorder was examined in 557 bipolar patients and 725 controls (all personally interviewed), recruited from seven countries (Belgium, Bulgaria, Croatia, Germany, Greece, Italy, and UK). The frequencies of the eight alleles that were identified did not differ between patients and control individuals in the whole population, while the power to detect an association based on our sample was relatively high. Some differences were noted among the various ethnic groups, but no significant trends existed, suggesting that population stratification by country may not be responsible for a type II error. On the basis of these results, mutations of the phospholipase A2 gene, at least in the region close to the polymorphism examined between exons 1 and 2, are not involved in the pathogenesis of bipolar mood disorder.

Objective: The aim of this article is to critically review all published studies regarding the efficacy and safety of the concurrent administration of clozapine (CLZ) and electroconvulsive therapy (ECT) in CLZ-resistant schizophrenic or schizoaffective patients., Method: A MEDLINE search from January 1980 to July 2005 was conducted., Results: One open-label trial and 6 case studies were located, comprising 21 schizophrenic and 1 schizo affective patients (12 men and 10 women) with a mean age of 41.9 years. The duration and dosage of CLZ monotherapy before ECT were reported at least 12 weeks and 300 mg/d, respectively, in 10 patients (45.4%). Plasma CLZ levels before ECT were assessed in 12 patients (54.5%), in which only 7 (31.8%) were reported to be higher than 350 ng/mL. The CLZ dosage during ECT ranged from 200 to 900 mg/d (mean, 518.2 +/- 203.3 mg/d). The number of ECT sessions ranged from 2 to 20 (mean, 11.5 +/- 5.4). Application of electrodes was unilateral in 7 patients, bilateral in 10 patients, and mixed in 2 patients. Sixteen patients (72.7%) showed marked improvement whereas 6 patients (27.3%) had moderate, minimal, or no improvement. No predictors of outcome could be isolated. Side effects reported by 5 patients (22.7%) were nausea, tachycardia, hypertension, memory problems, and confusion. Ten patients (45.4%) relapsed during follow-up. Substantial improvement persisted beyond 4 months in only 5 patients (22.7%)., Conclusion: Preliminary evidence exists for the safety and short-term efficacy of the concurrent administration of CLZ and ECT in CLZ-resistant schizophrenic or schizoaffective patients.

Dimensions of psychopathology and patterns of hostility, as well as the relationship of hostility to psychopathology, were studied in 85 male young adults: 41 with borderline personality disorder (BPD) and 44 with antisocial personality disorder (APD). Diagnoses were based on DSM-III. The following instruments were also used: Brief Psychiatric Rating Scale, Hamilton Depression Rating scale, State-Trait Anxiety Inventory, and Hostility and Direction of Hostility Questionnaire. BPD patients compared with APD patients showed higher levels of overall psychopathology and depression, whereas both groups had equally high anxiety. Total hostility was quite high in both groups. However, BPD patients had more introverted hostility and APD patients had more extroverted hostility. In BPD patients, introverted hostility was related to overall psychopathology, depression, and trait anxiety, whereas in APD patients, no significant relationship of any type of hostility to various dimensions of psychopathology was observed. In conclusion, when comprehensively assessed, BPD patients can be discriminated from APD patients based on certain dimensions of psychopathology and differences in the direction of their hostility. Moreover, the relationship between psychopathology and hostility patterns suggests that the direction of patients' hostility plays an important role in the development of disorder-specific symptomatology.

During the year their insomnia began, chronic insomniacs experienced a greater number of stressful life events compared with previous or subsequent years and compared with good sleepers. In addition, among the life event categories assessed, insomniacs reported a greater number of undesirable events, particularly events related to losses and to ill health. They also had lifelong histories of more illnesses and somatic complaints, beginning with more childhood illnesses and more childhood problems related to eating and sleeping. During childhood, insomniacs reported more frequent discontent with their families, and prior to the onset of insomnia, they had less satisfying relationships with their parents as well as problems in other interpersonal relations and in their self-concepts. Currently, insomniacs felt considerably less satisfied with their lives, had lower self-concepts, and had greater difficulty with interpersonal relationships. Thus, stressful life events, mediated by certain predisposing factors of personal vulnerability, were found to be closely related to the onset of chronic insomnia.

In a study designed to assess personality patterns of patients with chronic insomnia, a total of 528 subjects (428 insomniacs and 100 controls) completed the Minnesota Multiphasic Personality Inventory (MMPI). Comparison of the MMPI profiles of insomniacs from a semirural area and of those from an urban area, each in a completely different geographic region, showed results consistent for high levels of psychopathology as well as for specific personality patterns within and between groups. The personality patterns of insomniac subjects were remarkably homogeneous: only a few MMPI code types accounted for about one-half of each insomniac sample. The insomniac profiles were consistently characterized by the presence of neurotic depression, rumination, chronic anxiety, inhibition of emotions, and an inability to discharge anger outwardly. The results of this study confirm the original hypothesis that the handling of stresses and conflicts through an internalization of emotions leads to physiologic activation and is a major factor underlying the development and maintenance of chronic insomnia.