Second-generation antipsychotic use in schizophrenia and associated weight gain: a critical review and meta-analysis of behavioral and pharmacologic treatments.

BACKGROUND: Weight gain in schizophrenia, particularly secondary to second-generation antipsychotic (SGA) use, is a common adverse effect and often is associated with significant physical and psychological morbidity. METHODS: We performed a critical literature review of all controlled clinical trials for pharmacologic and/or behavioral management of SGA-induced weight gain in schizophrenia patients by searching PubMed and Google Scholar. A meta-analysis was performed to estimate and compare weight changes for various medications and behavioral interventions. RESULTS: Sample sizes generally were small. Clinical trials were 6 weeks to 1 year, and weight loss was modest with any treatment. Although several adjunctive pharmacologic treatments showed no weight loss, sibutramine, metformin, and topiramate showed some benefit. Amantadine and orlistat were somewhat less effective and had lower rates of tolerability. Among the behavioral therapies, nutritional counseling combined with exercise showed the most benefit. Behavioral therapies, although modest, showed the most consistent benefits compared with controls. CONCLUSIONS: Scheduled pharmacologic treatment to prevent weight gain or promote weight loss in schizophrenia patients on SGA therapy is limited based on current studies. Switching antipsychotic agents has not been established as a long-term solution. Additional long-term studies are required to influence clinical practice.

Psychotropics and sexual dysfunction: the evidence and treatments.

Sexual dysfunction is common in the general population and even more common in the mentally or medically ill. Because mentally ill patients often receive psychotropics, many of which affect sexual functioning, a patient's pre-existing sexual difficulties are often compounded, and these adverse effects may contribute to psychological difficulties or medication discontinuation. The effects of antidepressants, antipsychotics, mood stabilizers and anxiolytics on sexual functioning are critically reviewed. When possible, the types of sexual dysfunction (e.g. desire, arousal, or orgasm) induced by the drug is described. Treatments for drug-induced sexual function are described, but few controlled studies show benefit. Only sildenafil stands as a convincing treatment for drug-induced sexual dysfunction. The paper focuses on the placebo-controlled clinical trials that specifically evaluated sexual functioning in patients treated with psychotropics. Controlled studies are few for all the agents, though best for the antidepressants and antipsychotics. The exact magnitude and phase of sexual functioning affected remains to be elucidated for most psychotropic drugs. Although all phases of sexual functioning may be impaired by psychotropics, selective serotonin reuptake inhibitor antidepressants appear to primarily affect orgasm, while antipsychotics primarily affect desire. There is insufficient evidence to make conclusions about the anxiolytics or mood stabilizers.

Guidelines for the pharmacologic treatment of neurobehavioral sequelae of traumatic brain injury.

There is currently a lack of evidence-based guidelines to guide the pharmacological treatment of neurobehavioral problems that commonly occur after traumatic brain injury (TBI). It was our objective to review the current literature on the pharmacological treatment of neurobehavioral problems after traumatic brain injury in three key areas: aggression, cognitive disorders, and affective disorders/anxiety/ psychosis. Three panels of leading researchers in the field of brain injury were formed to review the current literature on pharmacological treatment for TBI sequelae in the topic areas of affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A comprehensive Medline literature search was performed by each group to establish the groups of pertinent articles. Additional articles were obtained from bibliography searches of the primary articles. Group members then independently reviewed the articles and established a consensus rating. Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems. Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI. Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI. The evidence-based guidelines and options established by this working group may help to guide the pharmacological treatment of the person experiencing neurobehavioral sequelae following TBI. There is a clear need for well-designed randomized controlled trials in the treatment of these common problems after TBI in order to establish definitive treatment standards for this patient population.

Antidepressant-related erectile dysfunction: management via avoidance, switching antidepressants, antidotes, and adaptation.

The ideal antidepressant would control depression with no adverse effect on sexual function. Erectile dysfunction and other sexual dysfunction associated with antidepressant medication treatment are problems with many antidepressants and can lead to patient dissatisfaction and decreased compliance with treatment. A computerized MEDLINE search (English language, 1966-2003) was performed using the terms antidepressive agents, erectile dysfunction, and sexual dysfunction. Emphasis was placed on studies with specific sexual function measurements taken before and after treatment and placebo control. Mixed mediator, nonserotonergic antidepressants that block postsynaptic serotonin type 2 receptors (nefazodone, mirtazapine) or that primarily increase dopamine or norepinephrine levels (bupropion) were thought to be good choices for avoiding antidepressant-associated sexual dysfunction or for switching patients in whom antidepressant-associated sexual dysfunction emerged. Comparisons with serotonin reuptake inhibitors (SRIs) have revealed less desire and orgasm dysfunction with nonserotonergic bupropion, less orgasm dysfunction with nefazodone, and superior overall satisfaction with sexual functioning with bupropion or nefazodone. However, most of these studies have design flaws that make evidence-based claims of efficacy difficult to substantiate. Agents proposed for antidote use in antidepressant-associated sexual dysfunction have either not been studied in men or not proved efficacious in randomized placebo-controlled trials. Switching to and augmentation with bupropion or nefazodone have also not clearly shown efficacy in controlled trials and require care and monitoring to avoid SRI discontinuation symptoms and loss of antidepressant efficacy. Few proposed treatment options, apart from avoidance, have proved effective for antidepressant-associated sexual dysfunction, which can have negative consequences on depression management.

Predictors of psychological symptoms 1 year after traumatic brain injury: a population-based, epidemiological study.

OBJECTIVE: To examine self-reported psychological symptoms 1 year after traumatic brain injury (TBI) in a population-based sample. PARTICIPANTS: There were 1560 adults who had sustained TBI. DESIGN: A telephone survey with questions about recent mood and anxiety symptoms, and diagnoses since TBI. Polychotomous logistic regression with 3 response levels (probable, possible, and no mood or anxiety symptoms) identified predictors of psychological symptoms. RESULTS: Overall, 40% of participants had clinically significant mood or anxiety symptoms-12.6% with probable symptoms and 27.5% with possible symptoms. Main risk factors for probable symptoms included younger age, poor physical functioning, inadequate social support, and being a white woman. Other risk factors included being retired or unemployed, and pre-TBI psychiatric disorder or multiple concussions. CONCLUSIONS: These findings suggest the need for careful screening of persons with TBI who are at particular risk of developing psychological symptoms, and persons who have recently sustained TBI and their families to be educated about the possibility of developing such symptoms.

Patterns of alcohol use 1 year after traumatic brain injury: a population-based, epidemiological study.

This study delineated patterns of alcohol use 1 year after traumatic brain injury (TBI) in a large, population-based, epidemiological, nonclinical sample, and identified predictors of heavy alcohol use in these individuals. Participants were 1,606 adults identified by review of a South Carolina statewide hospital discharge data set, on the basis of satisfying the Centers for Disease Control case definition of TBI, and were interviewed by telephone 1 year after TBI-related discharge. Alcohol use in the month prior to interview was classified according to categories from the Quantity-Frequency-Variability Index; heavy drinking was defined as nearly daily use with > or = 5 drinks at least occasionally, or at least three occasions with > or = 5 drinks. A polychotomous logistic regression with 3 response levels (heavy, moderate, and abstinent/infrequent/light drinking) was used to identify predictors of heavy drinking. Heavy drinking in the month prior to interview was reported by 15.4% of participants, while 14.3% reported moderate drinking and 70.3% reported abstinence or light/infrequent drinking. Risk factors for heavy drinking included male gender, younger age, history of substance abuse prior to TBI, diagnosis of depression since TBI, fair/moderate mental health, and better physical functioning. There was no association between drinking patterns and TBI severity.

Psychosis and delirium following metabolife use.

Weight gain is a well-known complication of antipsychotic therapy, especially when using newer atypical antipsychotic agents. In addition to the risk of medical comorbidities associated with weight gain, such as diabetes mellitus and cardiovascular disease, a further risk of antipsychotic-induced weight gain is that patients may resort to over-the-counter preparations to aid in weight loss. We report on a case in which a patient with schizophrenia began using Metabolife, an herbal preparation containing ephedra, for weight reduction and subsequently developed an exacerbation of his psychosis with superimposed delirium. We mention several relatively safe alternatives to herbal supplements for weight loss, as well as emphasize the need for clinicians to educate their patients regarding the potential risks of over-the-counter weight loss agents.

Does comorbid anxiety or depression affect clinical outcomes in patients with post-traumatic stress disorder and alcohol use disorders?

Post-traumatic stress disorder (PTSD) is commonly comorbid with other psychiatric disorders, including substance use disorders. In spite of this, pharmacologic treatment trials for PTSD often exclude individuals with significant psychiatric comorbidity. This study is a post hoc analysis of a 12-week double-blind placebo-controlled trial investigating sertraline in the treatment of patients with comorbid PTSD and an alcohol use disorder. Individuals with additional anxiety and affective disorders were included. Patients (N = 93) were stratified into four groups depending on presence or absence of additional anxiety or depressive disorders and evaluated for the effects of comorbidity on PTSD symptoms, depressive symptoms, and drinking behaviors. We hypothesized that additional comorbidity would be associated with poorer outcomes. Patients in all four subgroups showed marked and clinically significant improvement in alcohol drinking behaviors over the course of the study. For the entire sample, over the course of the 12 weeks, mean drinks per drinking day fell from 13.0 +/- 8.4 (SD) to 3.0 +/- 5.0 (SD); t = 10.2, df = 92, P <.000. There were, however, no significant differences among groups. Patients in all four groups showed moderate improvement in Hamilton Depression Rating Scale (HAMD) scores and Clinician-Administered PTSD scale (CAPS) scores at endpoint. For the entire sample, mean CAPS scores fell from 59.3 +/- 19.4 (SD) to 40.8 +/- 26.0, t = 8.9, df = 92, P <.000. Mean HAMD scores fell from 17. 9 +/- 6.7 (SD) at baseline to 11.8 +/- 9.4 (SD) at endpoint; t = 6.7, df = 92, P <.000. There were, however, no significant differences among groups for change in HAM-D or CAPS scores. Hence, contrary to our hypothesis, having additional anxiety or mood disorder comorbidity did not decrease treatment response in individuals with comorbid PTSD and an alcohol use disorder.