January 2010

Asenapine to Treat Schizophrenia and Bipolar Disorder
The new antipsychotic asenapine (Saphris) appears comparable to other second-generation agents but requires sublingual administration.

Clozapine Plus Other Antipsychotics
A paper by Taylor and Smith suggests that adding another antipsychotic to clozapine (Clozaril and others) for treatment-resistant patients has minimal therapeutic benefit.

Isotretinoin (Accutane) May Exacerbate Symptoms in Patients with Bipolar Disorder
Isotretinoin (Accutane) may destabilize mood in patients with bipolar disorder.

Stimulants Associated with Sudden Death in Young Patients
Stimulants such as methylphenidate may increase the risk of sudden unexplained death in young patients.

In Brief
Depression Risk Lower with 'Whole Foods' Diet; Anxiety during Menopause Not Improved by Black Cohosh

Lithium, Thyroid Function, and Depressive Relapse
Patients with bipolar disorder treated with lithium may develop depressive episodes due to changes in thyroid function.

Fighting Fire with Fire: Injectable Heroin for Heroin Addicts?
Diacetylmorphine merits consideration as a treatment of last resort for heroin addicts who don’t respond to methadone therapy.

Lithium, Thyroid Function, and Depressive Relapse

January 2010

Lithium remains a mainstay of treatment for patients with bipolar disorder. Although many patients fail to improve with lithium, have difficulty tolerating it, or need adjunctive therapy to stabilize their mood, a genetically homogeneous subset of patients with bipolar disorder may benefit uniquely from this inexpensive agent.

Among its many adverse effects, lithium can suppress thyroid function. A marker of diminished thyroid function is elevated thyroid-stimulating hormone (TSH). In a previous 12-month double-blind trial, Frye and coworkers found that when mean serum free T4 levels were lower, lithium-treated patients with bipolar disorder were more likely to suffer a mood episode and also to have more severe depressive symptoms (both P < .01).1 This thyroid-mood link led Frye and colleagues to conduct an exploratory post-hoc analysis of data from two randomized, double-blind trials.2 The two 18-month studies, funded by GlaxoSmithKline, involved 109 subjects on maintenance treatment with lamotrigine (Lamictal), lithium, or placebo. All subjects enrolled in these trials had serum TSH within the normal limits at the time of enrollment.

Compared to patients treated with lamotrigine or placebo, those who took lithium had a higher adjusted group mean TSH and a statistically significant adjusted mean TSH change from their screening levels at week 52 (P < .001 and P < .05, respectively). Three subjects—all receiving lithium—developed TSH levels that were above normal. Among lithium-treated subjects, those who required treatment for a depressive episode had a statistically significantly increased adjusted group mean TSH (P = .017) compared with those who did not require depression treatment. This was not the case for patients who required treatment for depression in the lamotrigine or placebo groups, nor was it observed in patients who developed manic episodes.

The authors point out that the relationship among lithium treatment, thyroid function, and depression symptoms has been insufficiently studied. Since the data reported here are retrospective, conclusions must remain tentative. Nonetheless, the clinical take-home point is that if a patient taking lithium develops new or worsening symptoms of depression, measure thyroid function, along with a lithium level.

1Frye MA, Denicoff KD, Bryan AL, Smith-Jackson EE, Ali SO, Luckenbaugh D, Leverich GS, Post RM: Association between lower serum free T4 and greater mood instability and depression in lithium-maintained bipolar patients. Am J Psychiatry 1999;156:1909-1914.

2Frye MA, Yatham L, Ketter TA, Goldberg J, Suppes T, Calabrese JR, Bowden CL, Bourne E, Bahn RS, Adams B: Depressive relapse during lithium treatment associated with increased serum thyroid-stimulating hormone: Results from two placebo-controlled bipolar I maintenance studies. Acta Psychiatr Scand 2009;120:10-13.