Benzodiazepines Remain Important Therapeutic Options in Psychiatric Practice.

Benzodiazepines and medications acting on benzodiazepine receptors that do not have a benzodiazepine structure (z-drugs) have been viewed by some experts and regulatory bodies as having limited benefit and significant risks. Data presented in this article support the use of these medications as treatments of choice for acute situational anxiety, chronic anxiety disorders, insomnia, alcohol withdrawal syndromes, and catatonia. They may also be useful adjuncts in the treatment of anxious depression and mania, and for medically ill patients. Tolerance develops to sedation and possibly psychomotor impairment, but not to the anxiolytic effect of benzodiazepines. Sedation can impair cognitive function in some patients, but assertions that benzodiazepines increase the risk of dementia are not supported by recent data. Contrary to popular opinion, benzodiazepines are not frequently misused or conduits to misuse of other substances in patients without substance use disorders who are prescribed these medications for appropriate indications; most benzodiazepine misuse involves medications that are obtained from other people. Benzodiazepines are usually not lethal in overdose except when ingested with other substances, especially alcohol and opioids. Benzodiazepines comprise one of the few classes of psychotropic medication the mechanisms of action of which are clearly delineated, allowing for greater precision in their clinical use. These medications, therefore, belong in the therapeutic armamentarium of the knowledgeable clinician.

Calcium Channel Antagonists for Mood Disorders.

PURPOSE: Development of new thymoleptic medications has primarily centered on anticonvulsants and antipsychotic drugs. Based on our studies of intracellular calcium ion signaling in mood disorders, we were interested in the use of novel medications that act on this mechanism of neuronal activation as potential mood stabilizers. METHOD: We reviewed the dynamics of the calcium second messenger system and the international body of data demonstrating increased baseline and stimulated intracellular calcium levels in peripheral cells of patients with bipolar mood disorders. We then examined studies of the effect of established mood stabilizers on intracellular calcium ion levels and on mechanisms of mobilization of this second messenger. After summarizing studies of calcium channel blocking agents, whose primary action is to attenuate hyperactive intracellular calcium signaling, we considered clinical experience with this class of medications and the potential for further research. FINDINGS: Established mood stabilizers normalize increased intracellular calcium ion levels in bipolar disorder patients. Most case series and controlled studies suggest an antimanic and possibly mood stabilizing effect of the calcium channel blocking medications verapamil and nimodipine, with fewer data on isradipine. A relatively low risk of teratogenicity and lack of cognitive adverse effects or weight gain suggest possible applications in pregnancy and in patients for whom these are considerations. IMPLICATIONS: Medications that antagonize hyperactive intracellular signaling warrant more interest than they have received in psychiatry. Further experience will clarify the applications of these medications alone and in combination with more established mood stabilizers.

Predictors of later bipolar disorder in patients with subthreshold symptoms.

INTRODUCTION: The clinical significance of subthreshold bipolar disorder (SBD), which is characterized by an insufficient number or severity of hypomanic symptoms to qualify for a formal bipolar disorder diagnosis, remains to be determined. METHODS: We examined the outcomes three years later (2004-2005; Wave 2) of 40,512 civilian, non-institutionalized subjects who endorsed elation and/or irritability but did not meet full criteria for lifetime mania or hypomania in 2001-2002 (Wave 1). RESULTS: The likelihood of developing a clear episode of mania or hypomania by Wave 2 was significantly increased in subjects with elation or only irritability at Wave 1 compared with subjects who did not endorse either (OR 2.8, p<0.01 for each). Endorsement of both symptoms at Wave 1 increased the likelihood of a new episode of mania or hypomania 4.6 times, which was significantly higher than for those with only elation or irritability (p<.05 for each). LIMITATIONS: SBD was not limited to depression, reducing comparability to previous studies. Despite the large sample size, there were not enough subjects to determine the impact of different numbers and types of additional symptoms on bipolar outcome. Although the majority of subjects were followed between the two Waves, the total duration of follow-up was probably too short to determine the long-term conversion rate to mania or hypomania. CONCLUSIONS: Elation and/or irritability, especially if accompanied by trouble concentrating, racing thoughts or hyperactivity, may represent a prodrome of formal bipolar disorder that indicate close follow-up and cautious use of antidepressants.