Lithium: Updated Human Knowledge Using an Evidence-Based Approach : Part II: Clinical Pharmacology and Therapeutic Monitoring

Selecting a drug according to the treatment response in a relative has been widely accepted advice in the management of mood disorders. However, this recommendation has not been adequately substantiated in the literature. We tested the hypothesis that response to long-term lithium treatment is a familial trait. We compared response to long-term lithium treatment in bipolar relatives of bipolar lithium responders and bipolar controls. Twenty-four relatives with bipolar disorder (as determined using the Schedule for Affective Disorders and Schizophrenia-Lifetime version [SADS-L] and Research Diagnostic Criteria [RDC]) were identified in families of 106 patients with lithium-responsive bipolar disorder. A consecutive series of 40 lithium-treated patients in a bipolar clinic (meeting RDC and DSM-IV criteria for bipolar disorder) served as a comparison group. Lithium response was evaluated on a rating scale reflecting the quality and quantity of available data. The prevalence of unequivocal response among the relatives was 67%, as compared with the response rate of 35% in the comparison group (chi2 = 6.04, df = 1, p = .014). This highly significant difference in response between relatives and the control group supports the view that the response to lithium prophylaxis clusters in families.

In 2005, the Canadian Network for Mood and Anxiety Treatments (CANMAT) published guidelines for the management of bipolar disorder. This update reviews new evidence since the previous publication and incorporates recommendations based on the most current evidence for treatment of various phases of bipolar disorder. It is designed to be used in conjunction with the 2005 CANMAT Guidelines. The recommendations for the management of acute mania remain mostly unchanged. Lithium, valproate and several atypical antipsychotics continue to be recommended as first-line treatments for acute mania. For the management of bipolar depression, new data support quetiapine monotherapy as a first-line option. Lithium and lamotrigine monotherapy, olanzapine plus selective serotonin reuptake inhibitors (SSRI), and lithium or divalproex plus SSRI/bupropion continue to remain the other first-line options. First-line options in the maintenance treatment of bipolar disorder continue to be lithium, lamotrigine, valproate and olanzapine. There is recent evidence to support the combination of olanzapine and fluoxetine as a second-line maintenance therapy for bipolar depression. New data also support quetiapine monotherapy as a second-line option for the management of acute bipolar II depression. The importance of comorbid psychiatric and medical conditions cannot be understated, and this update provides an expanded look at the prevalence, impact and management of comorbid conditions in patients with bipolar disorder.

Bipolar disorder, overweight, and obesity are each national public health problems. Overweight and obesity also appear to be related to mood disorders, and patients with bipolar disorder, in particular, may be at greater risk for overweight and obesity than individuals in the general population. This risk may be due to factors associated with the illness itself and/or with medications used to treat bipolar disorder. We conducted a MEDLINE literature search of all English-language articles (1966-2002) using the keywords lithium, olanzapine, valproate, valproic acid, divalproex sodium, carbamazepine, lamotrigine, obesity, weight, and bipolar disorder. We augmented this search with manual review of relevant references. Our focus was on studies examining the prevalence of overweight and obesity in bipolar disorder, the risk and magnitude of weight gain associated with medications used to treat bipolar disorder, and the prevention and treatment of overweight and obesity in patients with bipolar disorder. Forty-five studies were reviewed. Patients with bipolar disorder appear to be at greater risk than the general population for overweight and obesity. Comorbid binge-eating disorder; the number of depressive episodes; treatment with medications associated with weight gain, alone or in combination; excessive carbohydrate consumption; and low rates of exercise appear to be risk factors for weight gain and obesity in patients with bipolar disorder. More research is required to identify the impact of specific risk factors for overweight and obesity in patients with bipolar disorder. These data could be used to develop better weight gain prevention and treatment programs for those with bipolar disorder. Therapeutic options include dietary counseling, use of mood stabilizers with lower propensities for weight gain, and combination pharmacotherapy with medications that have weight loss properties.