Kimberly H. Littrell

Weight Loss with Topiramate

TO THE EDITOR: The novel anticonvulsant topiramate has demonstrated efficacy in the treatment of adults with epileptic disorders.1,2 Although systematic, controlled studies are yet to be reported, there is preliminary evidence that topiramate is an effective mood stabilizer3,4 and may also mitigate pathologic weight gain.4-6 This latter action may be of value in the management of weight gain induced by novel (atypical) antipsychotic agents.7,8 We report a patient whose significant weight gain during olanzapine therapy was normalized by topiramate. Case Report. A 32-year-old white woman (height 5’8”) with a 16-year history of Diagnostic and Statistical Manual of Mental Disorders, 4th edition9– defined schizoaffective disorder had experienced intermittent binge eating, with weight fluctuations of up to 9 kg, since age 20. A routine medical examination diagnosed mild hypothyroidism at age 28, which had been successfully treated with levothyroxine. The patient had persistently normal thyroid indices until initiation of treatment with olanzapine 20 mg/d at age 29. She had previously been treated with several antipsychotic agents, including clozapine, with only modest success. At the initiation of olanzapine, the patient weighed 63.6 kg, with a body mass index (BMI) of 21.3. Over the next three years, she gained 36 kg, without evidence of fluid retention. After olanzapine initiation, the patient reported a recurrence of binging episodes, primarily of carbohydrates, occurring each afternoon and at night. She received monthly counseling on the roles of diet and exercise in weight management; these interventions, however, proved ineffective. During the first year of olanzapine treatment, the woman gained an average of 1 kg per month (total 12.2 kg). This weight gain continued during the second year, with an average gain of 0.6 kg per month (total 6.8 kg). During the third year, the patient’s rate of weight gain increased to an average of 1.5 kg per month (total 17.3 kg). At 90.9 kg, she experienced decreased control of her hypothyroidism. As a result, her endocrinologist increased the levothyroxine dosage to maintain normal thyroid-stimulating hormone concentrations. Her final weight at the end of the three-year period was 100 kg, raising her BMI to 33.5. Despite good control of psychotic symptoms, the patient reported mood swings, depression, and subjective distress regarding her weight gain. In view of the clinical features, she was treated with topiramate for both mood stabilization and to aid in weight normalization. At topiramate initiation, the woman continued to be unable to implement any nonpharmacologic interventions to lose weight. Concomitant medications included olanzapine and levothyroxine, which remained at stable doses throughout the topiramate trial. Topiramate was initiated at 25 mg/d and titrated up to 150 mg/d within two weeks. Within the first four weeks of treatment with topiramate, the woman reported a dramatic decrease in binging episodes to two to four times per month, which remained at this frequency throughout treatment. The patient lost an average of 2.3 kg per week during the initial eight weeks of treatment. After 10 weeks, the topiramate dosage was decreased to 75 mg/d due to difficulty in concentration. She remained on this dosage for an additional 32 weeks and lost a total of 30.9 kg. Her weight loss reached a plateau at 32 weeks and remained unchanged from week 32 to week 42. She subsequently requested topiramate discontinuation. The patient experienced a significant reduction in mood swings, crying, and depression during topiramate treatment. After topiramate discontinuation, she initiated behavior modification efforts to maintain her weight loss, ostensibly because she now felt that it was realistic to maintain her reduced weight, in contrast to her previous feelings of hopelessness concerning weight management. The woman began to monitor her caloric intake, participated in aerobic exercise, and initiated behavior modification techniques (trigger avoidance, food substitution) to control her binge eating. Six months after topiramate discontinuation, she had maintained an average weight of 70.5 kg (BMI 23.6) while continuing to receive olanzapine 20 mg/d. Both her psychotic and mood symptoms remained under excellent control. Discussion. This case report provides preliminary evidence that may support a pharmacologic intervention for antipsychotic-induced weight gain in someone who was initially unwilling, or unable, to follow conventional diet strategies. Shapira et al.10 have hypothesized that topiramate’s antagonism of kainate/AMPA glutamate receptors subtypes may cause appetite suppression, leading to a reduction in binge-eating behavior, which is precisely what we observed. The patient tolerated topiramate for an extended period of time (>10 mo) achieving a steady, continued weight loss for 32 weeks. Controlled clinical trials are needed to determine the efficacy and safety of combining topiramate with antipsychotic agents.

Current understanding of violence and aggression: assessment and treatment.

Links between violence, aggression, and mental illness are well documented. Despite this association, our current understanding of the causation and optimal treatment of aggression remains limited. This lack of knowledge is alarming because nurses treating patients with mentally illness are frequent targets of patient aggression. Consequently, the aim of this article is to provide contemporary information regarding the concept of patient aggression, assessment of violent behavior, and implementation of treatment interventions. A review of pharmacological and psychosocial strategies are presented as well. These findings provide psychiatric nurses with a conceptual model as well as practical interventions for patient aggression.

Olanzapine: a 5-year perspective.

Olanzapine is a novel antipsychotic, approved for the acute and maintenance treatment of schizophrenia and bipolar I disorder. Despite the publicity regarding reported adverse events with the novel antipsychotics, such as weight gain and Type II diabetes mellitus, olanzapine remains a useful and important medicine. It is a selective monoaminergic antagonist with high-affinity binding to a number of receptors thought to be implicated in some psychotic and mood symptoms. The complex pharmacology of olanzapine has lead to studies exploring its use in treating substance abuse, aggression/violence, borderline personality disorder, schizotypal personality disorder, obsessive–compulsive disorder and as a neuroprotective agent in schizophrenia. As the pharmacology of olanzapine and other novel antipsychotics becomes better understood, future effective treatment strategies are likely to match an individual’s genetic makeup and receptor profiles to the most compatible agent.

Schizophrenia and Comorbid Substance Abuse

Abstract Research suggests that nearly half of all patients with schizophrenia concurrently abuse substances. However, despite the prevalence of substance abuse among persons with schizophrenia, the effective treatment of these comorbid conditions has eluded mental health professionals for decades. Apart from the obvious problems associated with schizophrenia and alcohol or drug abuse, schizophrenic persons who abuse substances also experience increased rates of depression, suicide, homelessness, unemployment, and illegal activity. These diverse problems necessitate interventions that address the special needs of this population. Research indicates that the use of atypical antipsychotic agents with persons who have a dual diagnosis may prove to be efficacious with treatment, overall. This article reviews the current literature pertaining to the potential expanded therapeutic benefits of enhanced efficacy of atypical antipsychotic medication in association with decreased substance use and craving.

Managing Aggression in Schizophrenia

Abstract Agitation and aggression are frequent behavioral manifestations of persons diagnosed with a psychiatric illness. Data from the Epidemiological Catchment Area study indicate that persons with schizophrenia have a four-fold increase for the risk of violent behavior in a 1-year period. Additional research indicates that acute psychosis is a consistent risk factor for the occurrence of violence; approximately 10% of patients diagnosed with schizophrenia display assaultive behavior within 2 weeks before hospital admission. In addition, 20% to 30% of patients who display psychotic symptoms engage in threats, verbal aggression, and property damage within the same period. Once hospitalized, 10% to 15% of these patients become physically assaultive, and 30% to 35% engage in fear-inducing behaviors. Clearly, the management of aggression in patients with schizophrenia is an important consideration for nurses working with this population.

Choosing an antipsychotic in the treatment of schizophrenia: Conversions to olanzapine

Abstract The recent introduction of olanzapine (Zyprexa) has provided another first-line antipsychotic treatment option in the pharmacologic treatment of psychiatric patients. Unlike clozapine which is restricted to use with refractory schizophrenia, olanzapine is labeled for the management of manifestations of psychotic disorders . This implies a much larger potential treatment population besides schizophrenia, and nurses should consider its use beyond patients with treatment-resistant schizophrenia. Matters of therapeutic dosing, titration, and maintenance dosing are remarkably simple with this compound. With the current availability of olanzapine, nurses will need to be familiar with the issues surrounding conversion from other antipsychotic agents to this new agent.

Therapeutic efficacy of olanzapine

Abstract The evaluation of efficacy of antipsychotic medications is a complex process. For more than 40 years conventional antipsychotic agents have formed the cornerstone of treatment for patients with schizophrenia. During this period the marker for therapeutic effectiveness has focused almost exclusively on the control of psychotic symptoms. Now with the introduction of atypical antipsychotic agents it seems possible to achieve control of symptoms in multiple domains. Clinical trials of the new antipsychotic, olanzapine (Zyprexa), demonstrated control of both positive and negative symptoms of schizophrenia and comorbid depressive symptoms. Olanzapine appeared to be significantly better than haloperidol in maintaining symptom remission and preventing relapse. Recently approved by the Food and Drug Administration as a first-line agent for the treatment of psychosis, olanzapine has demonstrated enhanced efficacy for use in both acute and maintenance treatment modalities. This article reports results from a 6-week open label trial of the drug. Significant improvements were found. Findings are limited by small sample size. However, the early positive results encourage both further testing and challenge nurses to expand their skills in assisting patients and their families with the recovery process.

Emerging applications of newer antipsychotic agents in specific patient populations

Abstract Conventional neuroleptics have been the mainstay of treatment for patients with schizophrenia for many years. The mechanism of action of these drugs has long been accepted and their side effects well documented. With the recent introduction of newer antipsychotics such as clozapine, risperidone, and olanzapine, a new generation of medications has become available whose pharmacologic properties are just beginning to be realized. These newer antipsychotics appear to be superior to conventional neuroleptics in treating patients with schizophrenia. Because of their reduced neurotoxicity, the newer antipsychotics may be particularly beneficial in treating psychosis in specific patient populations. This review presents preliminary findings on the use of the newer antipsychotics for treating psychosis in five patient populations: children and adolescents with schizophrenia and other psychotic disorders; first-episode schizophrenia; dual diagnosis; bipolar disorder; and elderly patients. Because of the expanded utilities of the newer antipsychotics, psychiatric nurses should be familiar with all available treatment options.

Recent advances in the understanding of negative symptoms in schizophrenia

Abstract The aim of this article is to provide a comprehensive and concise review of existing literature and findings about negative symptoms associated with the diagnosis of schizophrenia. Significant progress has been made regarding the awareness of negative symptoms associated with schizophrenia. Given this progress, psychiatric nurses should find it useful to have information about how to provide state-of-the-art care and clinical interventions for treatment of negative symptoms. Acquiring this information requires some understanding of etiologic factors, assessment, and use of contemporary medications to attend to the disabling effects of negative symptoms.