John Cookson

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder

BACKGROUND Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.

Prolactin, hyperprolactinaemia and antipsychotic treatment: a review and lessons for treatment of early psychosis

Hyperprolactinaemia is a common side effect of antipsychotics; markedly raised levels are less common. Higher levels of prolactin result from longer exposure to higher doses, especially with older antipsychotics or with risperidone, sulpiride or amisulpride. Galactorrhoea, gynaecomastia, menstrual abnormalities and sexual dysfunction including hypogonadism and fertility problems are consequences of raised prolactin, and in the longer-term bone demineralisation. Younger patients may be more susceptible to hyperprolactinaemia. Trial reports often fail to state the frequency of raised levels.

Carbamazepine compared to haloperidol in acute mania.

In a double-blind, between-patient clinical trial carbamazepine (CBZ) (n = 8) was compared to haloperidol (HP) (n = 9) in patients presenting with mania (DSM III). Seven patients on HP and 2 on CBZ failed to complete 4 weeks treatment. In 4 of the HP group this was because of extrapyramidal side-effects (EPS). Two patients on CBZ and 2 on HP were withdrawn because of lack of efficacy. Statistically significant clinical improvement was seen in both groups within the first 2 weeks of treatment with HP acting more quickly. In addition to EPS which occurred in HP patients, drowsiness was experienced in 4 on CBZ and 3 on HP, and gastrointestinal symptoms in 3 on CBZ. No serious haematological changes, nor abnormalities in clinical chemistry occurred in either group. We conclude that CBZ appears to be a potentially useful drug in the treatment of acute mania.

Relationship of suicide rates to economic variables in Europe: 2000-2011

BACKGROUND It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Treatment benefits of duloxetine in major depressive disorder as assessed by number needed to treat.

The efficacy of an antidepressant typically is assessed by comparing it with placebo using a validated rating scale. This type of analysis, however, does not translate well to the clinical settings. For clinicians, a more meaningful measure is the number needed to treat (NNT). The objective of this analysis is to assess the efficacy of duloxetine in terms of NNT. Data were obtained from nine clinical trials designed to assess the efficacy and safety of duloxetine as a treatment for major depressive disorder. These studies examined 8–9 weeks of acute treatment with duloxetine. NNT estimates were determined for duloxetine, selective serotonin reuptake inhibitor comparators from six multi-dose studies, and for duloxetine in patients ≥65 years of age. The NNT was based on the Hamilton Depression Rating Scale (HAMD17) for response and remission, and improvements defined by the Clinical Global Impression (CGI) were estimated and compared. The NNT was favorable for both duloxetine and selective serotonin reuptake inhibitor compared with placebo. The patients receiving duloxetine had NNT for HAMD17 response of 6.0, remission 7–9, and CGI-defined improvement 6–7 by 8 weeks. The NNTs for selective serotonin reuptake inhibitors (fluoxetine or paroxetine, 20 mg/day) were around 7 for response, 11 for remission, and 8 for CGI-defined improvement. The NNTs in the elderly were similar. The NNT for several measures of efficacy including remission consistently demonstrated the treatment benefits of duloxetine as well as of fluoxetine and paroxetine compared with placebo.

Positive and negative symptoms, depression and social disability in chronic schizophrenia: a comparative trial of bromperidol and fluphenazine decanoates.

A 1 year double-blind trial of bromperidol decanoate and fluphenazine decanoate was conducted in the maintenance treatment of 47 outpatients with schizophrenia. Six patients relapsed on bromperidol decanoate and none on fluphenazine decanoate, a difference which is statistically significant. No significant differences in positive and negative symptoms, nor depression measures were found between treatment groups when comparisons were made for change in score from entry to last visit. However, patients on fluphenazine decanoate achieved significantly better changes on social disability (Morningside scale) compared to those on bromperidol decanoate. The incidence of extrapyramidal side-effects was similar in both groups, and no statistically significant differences emerged in body weight change between treatments.

The effects of methylamphetamine on mood and appetite in depressed patients: a placebo-controlled study.

Methylamphetamine given intravenously as a single 15 mg dose led to a pronounced elevation of mood in 7 out of 21 depressed patients compared to a control injection of sterile water administered on another occasion in random order under double-blind conditions. All 7 responders experienced an increase of VAS self-ratings of hunger in contrast to what has been observed in normal subjects who show a decrease in hunger after amphetamine. The implications of these findings are discussed in the light of monoamine theories of depression and appetite control.

The use of anticonvulsants in the aftermath of mania

This paper reviews the evidence for the efficacy of anticonvulsants in the continuation and maintenance phases of treatment of bipolar disorder, when there has been an episode of mania (Bipolar-I disorder). The evidence to be considered is primarily that arising from randomized controlled trials. A literature search was performed to identify all randomized controlled trials of anticonvulsants used as maintenance treatment for bipolar-I disorder. Placebo-controlled studies were preferred, however there have been relatively few of these and clinical practice must therefore be guided by evidence carrying a lower level of conviction. Valproate monotherapy lacks a convincing evidence base. The view that valproate is more effective than lithium in rapid cycling has not been borne out. Lamotrigine is effective in preventing depression after an episode of mania. As monotherapy, lithium appears superior to carbamazepine in bipolar patients not previously treated with either drug. The combination of lithium and carbamazepine may be superior to either drug alone, in certain treatment-resistant patients, but is associated with increased side effects. Other anticonvulsants lack evidence supporting their use in bipolar disorder except in treating co-morbid alcohol dependence, anxiety and bulimic symptoms. Valproate continues to be recommended by most current guidelines despite the lack of evidence.

Toward a clinical understanding of bipolar disorders : Classification and presentation

Summary:  This review describes the clinical spectrum of bipolar disorder and its classification in the Diagnostic and Statistical Manual of Mental Disorders (DSM)‐IV and the International Classification of Diseases (ICD)‐10. The development of new diagnostic trends and their clinical implications are discussed.

Menstrual cycle effects on the action of buspirone on food intake in healthy female volunteers.

We studied the effect of single doses of the 5-HT1A agonist buspirone (10 mg and 20 mg) on food intake during the menstrual cycle of nine healthy women, none of whom were on a contraceptive pill. In a double-blind placebo-controlled trial, subjects were tested over three cycles, receiving one treatment per cycle. Within each cycle, they were tested at two time points; mid-follicular and late luteal. Food intake following 20 mg buspirone was significantly higher in the luteal phase, suggesting the possibility of pre-menstrually enhanced 5-HT receptor sensitivity.