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Background: Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications., Aim: To explore whether the decreased body weight in these patients is associated with a worsened psychopathology., Methods: In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test., Results: Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores., Conclusions: Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.

Background: An increased amount of deep sleep has been shown to be associated with antisocial personality disorder. This phenomenon has also been observed in a habitually violent female offender with schizophrenia and alcohol dependence., Aim: To evaluate sleep patterns in this patient and compare them with those of healthy, pro-social women of similar age, and in the same patient over time after treatment., Method: Multiple measures of sleep were taken over two consecutive nights with the presenting patient and with three age-matched healthy women. One year after the patient was established on atypical antipsychotic (quetiapine), and antidepressant (SSRI) medication (citalopram) her sleep evaluation was repeated. In each case only the second night's recordings were used in analyses., Results: The patient differed significantly from the three healthy women on most sleep measures. After a year on the medication, the patient's sleep had improved and the non-REM sleep measures had come into the normal range. She had also shown a sustained clinical and behavioural improvement., Discussion and Implications: The literature suggests that both drugs had a part to play in the improvements in sleep, symptomatology and behaviour. The possibility that improvement in deep sleep is secondary to citalopram and that it is this that was specifically associated with violence reduction seems worthy of further study.

Objective: We tested the hypothesis that topiramate is more effective than placebo in reducing symptoms in patients with treatment-resistant schizophrenia when combined with ongoing antipsychotic medication., Method: Twenty-six hospitalized treatment-resistant patients with chronic DSM-IV-diagnosed schizophrenia participated in a randomized, double-blind, placebo-controlled trial in which 300 mg/day of topiramate was gradually added to their ongoing treatment (clozapine, olanzapine, risperidone, or quetiapine) over two 12-week crossover treatment periods. Data were collected from April 2003 to November 2003., Results: In intention-to-treat analysis, topiramate was more effective than placebo in reducing Positive and Negative Syndrome Scale general psychopathologic symptoms (effect size = 0.7, p = .021), whereas no significant improvement was observed in positive or negative symptoms., Conclusion: Glutamate antagonist topiramate may be an effective adjuvant treatment in reducing general psychopathologic symptoms in patients with schizophrenia resistant to treatment with second-generation antipsychotics.

Background: Psychiatric sleep research has attempted to identify diagnostically sensitive and specific sleep patterns associated with particular disorders. Both schizophrenia and alcoholism are typically characterized by a severe sleep disturbance associated with decreased amounts of slow wave sleep, the physiologically significant, refreshing part of the sleep. Antisocial behaviour with severe aggression, on the contrary, has been reported to associate with increased deep sleep reflecting either specific brain pathology or a delay in the normal development of sleep patterns. The authors are not aware of previous sleep studies in patients with both schizophrenia and antisocial personality disorder., Case Presentation: The aim of the present case-study was to characterize the sleep architecture of a violent, medication-free and detoxified female offender with schizophrenia, alcoholism and features of antisocial personality disorder using polysomnography. The controls consisted of three healthy, age-matched women with no history of physical violence. The offender's sleep architecture was otherwise very typical for patients with schizophrenia and/or alcoholism, but an extremely high amount of deep sleep was observed in her sleep recording., Conclusions: The finding strengthens the view that severe aggression is related to an abnormal sleep pattern with increased deep sleep. The authors were able to observe this phenomenon in an antisocially behaving, violent female offender with schizophrenia and alcohol dependence, the latter disorders previously reported to be associated with low levels of slow wave sleep. New studies are, however, needed to confirm and explain this preliminary finding.

In a double-blind, controlled study, we examined the therapeutic effects of high-frequency left prefrontal repetitive transcranial magnetic stimulation (rTMS) on schizophrenia symptoms. A total of 22 chronic hospitalized schizophrenia patients were randomly assigned to 2 weeks (10 sessions) of real or sham rTMS. rTMS was given with the following parameters: 20 trains of 5-second 10-Hz stimulation at 100 percent motor threshold, 30 seconds apart. Effects on positive and negative symptoms, self-reported symptoms, rough neuropsychological functioning, and hormones were assessed. Although there was a significant improvement in both groups in most of the symptom measures, no real differences were found between the groups. A decrease of more than 20 percent in the total PANSS score was found in 7 control subjects but only 1 subject from the real rTMS group. There was no change in hormone levels or neuropsychological functioning, measured by the MMSE, in either group. Left prefrontal rTMS (with the used parameters) seems to produce a significant nonspecific effect of the treatment procedure but no therapeutic effect in the most chronic and severely ill schizophrenia patients.

Background: There is no evidence from randomized, controlled trials that demonstrate effectiveness for any pharmacological treatment in clozapine-resistant schizophrenia. Since the introduction of chlorpromazine, all antipsychotics with proven efficacy on positive symptoms have been dopamine antagonists, but recent experimental data suggest that ketamine-induced positive schizophreniform symptoms in healthy subjects can be controlled by a glutamate antagonist lamotrigine. The hypothesis tested was that lamotrigine is more effective than placebo in the treatment of positive schizophrenic symptoms when combined with clozapine., Methods: Thirty-four hospitalized treatment-resistant patients having chronic schizophrenia participated in a double-blind, placebo-controlled, 14-week, crossover trial where 200 mg/day lamotrigine was gradually added to their ongoing clozapine treatment. Clinical assessments were made by the Positive and Negative Syndrome Scale at the beginning and end of each treatment period., Results: In intention-to-treat analysis, lamotrigine treatment was more effective in reducing positive (effect size.7, p =.009) and general psychopathological (effect size.6, p =.030) symptoms, whereas no improvement was observed in negative symptoms., Conclusions: These results provide the first evidence from a randomized controlled trial of an effective pharmacological treatment with an anticonvulsant agent in treatment-resistant schizophrenia and indicate that both positive and general psychopathological symptoms in patients with schizophrenia can be controlled by a drug that is not a dopamine antagonist. The results are in line with previous experimental data suggesting that excessive glutamate neurotransmission contributes to the positive symptoms of schizophrenia.

It is generally thought that schizophrenia does not predispose subjects to homicidal behavior. However, many previous studies have suffered from notable methodological weaknesses. In particular, obtaining comprehensive study groups of violent offenders has been difficult. Finnish police have been able to solve about 97 percent of homicides during the last few decades. Because most homicide offenders are subjected to intensive forensic psychiatric examination, we were able to obtain data for 93 homicide offenders with schizophrenia among 1,423 arrested during a 12-year period. Calculations of the odds ratios revealed that the risk of committing a homicide was about 10 times greater for schizophrenia patients of both genders than it was for the general population. Schizophrenia without alcoholism increased the odds ratio more than 7 times; schizophrenia with coexisting alcoholism more than 17 times males.