108 HANDBOOK OF PSYCHIATRIC DRUGS
108 HANDBOOK OF PSYCHIATRIC DRUGS
If lithium needs to be discontinued for any reason, it is preferable to taper the medication over six or more weeks. Rapid discontinuation increases the risk of relapse and may further increase the risk of suicidal actions.
It can be very difficult to determine whether a symptom, such as a minor drop in mood or several days of reduced sleep, represents a transient fluctuation or is a harbinger of a major affective episode. Daily mood charting and close contact with patient can help in this determination and also provide the opportunity to rapidly respond to an incipient relapse. Mild hypomanic symptoms may be more likely to be predic- tive of a manic relapse than depressive symptoms predictive of a recurrence of major depression. As described above, opti- mizing current medications and adding adjunctive treatments (e.g., benzodiazepine in a patient who feels slightly agitated and is not sleeping well) may be sufficient to prevent a more dramatic worsening in mood.
ANTICONVULSANTS Valproate is an important alternative to lithium as a main- tenance treatment for bipolar disorder. It may be prefer- able for patients with rapid cycling, a history of dysphoric or mixed mania, comorbid substance abuse or anxiety disor- ders, or organic brain disease. Carbamazepine has a some- what greater medical risk, in terms of bone marrow suppres- sion, but may be better tolerated than valproate for some patients. In clinical trials, approximately 60% of patients have
a moderate or marked response to carbamazepine compared with 22% with placebo. In comparisons with lithium, carba- mazepine was associated with equivalent or greater rates of improvement. Although no head to head comparisons exist for valproate and carbamazepine in maintenance treatment, other clinical data and experience suggest that they are compa- rably effective and work well in an overlapping subset of patients.
When valproate is used for maintenance therapy, it is best to start with a low dose, such as 250 to 500 mg daily, building the dose gradually to maintain a plasma level between 50 and
ated at a low dose, 100 mg/day, increasing in increments of
109 100 mg/day every four to five days. Dosing is usually two to four
MOOD STABILIZERS
times daily for the immediate release formulations. Although
a correlation between blood level and clinical response has yet to be established, most psychiatrists are guided by the thera-
Most patients taking carbamazepine for bipolar disorder are maintained with doses between 400 and 1800 mg/day. Because of enzyme induction, it is often necessary to increase the dose after two to three weeks of treatment to maintain the same blood level.
As described above, in the section on treatment of bipolar depression, two large maintenance trials evaluated lamot- rigine relative to lithium and placebo in remitted bipolar I and II patients. Lamotrigine was more robust in preventing relapse into depression and lithium was more robust in preventing relapse into mania, but both agents has some, albeit lower, efficacy in preventing the other phase (i.e., lithium for depression and lamotrigine for mania). As a broad mainte- nance regimen, it is certainly worth considering combining
a predominantly antidepressant mood stabilizer, such as lamotrigine with a predominantly antimanic one, such as lithium.