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.
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.
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.
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.
In response to increasing concerns about the potential influence of relationships with the pharmaceutical and device industry 1, academic medical centers (AMCs) began adopting conflict of interest ...(COI) policies in the 1990s 2. In the face of limited follow-up of initial alarm about the topic, we thought that it was timely to re-invigorate public discussion of the evaluation and management of the influence of COI on patient care, education, and research. ...employed physicians may have obligations to institutional patient flow requirements and potential bonuses that can conflict with optimal patient care, and all clinicians encounter financial incentives from third parties that can be in opposition to the best approach to the patient. Intellectual conflicts of interest 9 can occur when investigators whose reputations derive from a particular body of work review studies by authors with alternative ideas or when faculty members who promote a particular psychotherapy present this approach in consultations or lectures as the best of a group of therapies with equivalent empirical support.
Untreated mood and psychotic disorders can have substantial adverse impacts on the patient, the fetus and the family, while treatment can ameliorate such problems. To address concerns by clinicians ...about the risks of psychotropic medications, this review addresses the risk/benefit analysis of somatic therapies for psychiatric disorders during pregnancy and lactation. Areas covered: All available research was reviewed on the impact on pregnancy and breastfeeding of mood and psychotic disorders, and of antidepressants, mood stabilizers, antipsychotic drugs, and electroconvulsive therapy. References cited in other reviews, case series, formal studies, pharmacologic discussions, and theoretical pieces were added. Available case control and other studies were critically reviewed and diverse explanations for their findings were considered. Expert opinion: The potential benefits of treatment of mood and psychotic disorders often outweigh the risks after alternative therapies have been considered. Some medications, particularly paroxetine and valproate, pose greater risks during pregnancy, while the teratogenic risks of lithium have probably been overstated. There is more experience with first than with second generation antipsychotic drugs during pregnancy and lactation. Nursing an infant is possible while taking a number of antidepressants, mood stabilizers or antipsychotic drugs.
Pharmacogenomics, which is derived from genome-wide association studies (GWAS), and pharmacogenetics, which involves candidate gene association studies (CGASs), are proving increasingly useful in ...personalized cancer care. Research in psychiatric applications has primarily involved genetic polymorphisms of P450 CYP enzymes, which mediate oxidative metabolism, particularly CYP2D6, which is involved in the metabolism of at least 30 psychotropic medications. This work has been supplemented by genotyping of proteins for the drug efflux pump P-glycoprotein (P-gp), serotonin receptors, and the serotonin reuptake pump.
This review covers principles of pharmacogenetics and pharmacogenomics, previous analyses of pharmacokinetic and pharmacodynamics studies, newer studies of the predictive value of genetic testing in the treatment of depression, obstacles to implementation of genetic testing in predicting treatment response and side effects, and suggestions for future research.
Studies of multiple genes have produced some positive results in groups of patients, but genetic testing does not yet seem to be applicable to choosing medications for a specific patient.
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