Lithium Use During Pregnancy in a Patient With Bipolar Disorder and Multiple Sclerosis.

Although lithium is widely used as a first-line treatment for mood disorders, its mood-stabilizing effects remain not fully understood. A growing body of data are stressing that lithium seems to show broader properties, including neuroprotective effects. Lithium's ability to inhibit glycogen synthase kinase 3ß, an enzyme that participates in the phosphorylation of τ, a microtubule-associated protein, stimulated interest in its possible therapeutic role in Alzheimer disease and other neurodegenerative disorders. Preliminary data also support exploration of lithium's potential therapeutic role in multiple sclerosis, an autoimmune disorder that is associated with co-occurring mood disorders. Lithium is associated with teratogenic risks to the developing fetus; however, recently revised downward estimates of its teratogenic risk of causing fetal cardiac malformation suggest that its potential therapeutic benefit to both mothers with bipolar disorder and their offspring should be considered in at least some cases. A 43-year-old woman previously diagnosed with bipolar disorder and MS was treated with lithium and thyroid hormone supplementation as her sole medications during her pregnancy. The patient remained euthymic throughout her pregnancy and over the course of her 5-year follow-up evaluations on this medication regimen. In addition to her stable mood, there has been no symptomatic progression or relapse of her MS, and her daughter continues to develop normally.The case supports consideration of balancing lithium's mood-stabilizing benefit with its known teratogenic risk during pregnancy. The case also supports exploration of possible additional benefit in the context of MS co-occurring with bipolar disorder.

Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders.

BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women. CONCLUSIONS: Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study.