Kaplan + Sadock's Synopsis of Psychiatry, 11e

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29.12 Calcium Channel Blockers

Precautions and Adverse Reactions Buspirone does not cause weight gain, sexual dysfunction, dis- continuation symptoms, or significant sleep disturbance. It does not produce sedation or cognitive and psychomotor impairment. The most common adverse effects of buspirone are headache, nausea, dizziness, and (rarely) insomnia. No sedation is associ- ated with buspirone. Some persons may report a minor feeling of restlessness, although that symptom may reflect an incom- pletely treated anxiety disorder. No deaths have been reported from overdoses of buspirone, and the median lethal dose is estimated to be 160 to 550 times the recommended daily dose. Buspirone should be used with caution by persons with hepatic and renal impairment, pregnant women, and nursing mothers. Buspirone can be used safely by the elderly. Drug Interactions The coadministration of buspirone and haloperidol (Haldol) results in increased blood concentrations of haloperidol. Bus- pirone should not be used with MAOIs to avoid hypertensive episodes, and a 2-week washout period should pass between the discontinuation of MAOI use and the initiation of treatment with buspirone. Drugs or foods that inhibit CYP3A4, for exam- ple, erythromycin (E-mycin), itraconazole (Sporanox), nefazo- done (Serzone), and grapefruit juice, increase buspirone plasma concentrations. Laboratory Interferences Single doses of buspirone can cause transient elevations in growth hormone, prolactin, and cortisol concentrations, although the effects are not clinically significant. Dosage and Clinical Guidelines Buspirone is available in single-scored 5- and 10-mg tablets and triple-scored 15- and 30-mg tablets; treatment is usually initi- ated with either 5 mg orally three times daily or 7.5 mg orally twice daily. The dosage can be raised 5 mg every 2 to 4 days to the usual dosage range of 15 to 60 mg a day. Buspirone should not be used in patients with past hypersen- sitivity to buspirone, in cases of diabetes-associated metabolic acidosis, or in patients with severely compromised liver or renal function. Switching from a Benzodiazepine to Buspirone Buspirone is not cross-tolerant with benzodiazepines, barbi- turates, or alcohol. A common clinical problem, therefore, is how to initiate buspirone therapy in a person who is currently taking benzodiazepines. There are two alternatives. First, the clinician can start buspirone treatment gradually while the benzodiazepine is being withdrawn. Second, the clinician can start buspirone treatment and bring the person up to a thera- peutic dosage for 2 to 3 weeks while the person is still receiv- ing the regular dosage of the benzodiazepine and then slowly taper the benzodiazepine dosage. Patients who have received benzodiazepines in the past, especially in recent months, may find that buspirone is not as effective as the benzodiazepines in

the treatment of their anxiety. This might be explained by the absence of the immediate mildly euphoric and sedative effects of the benzodiazepines. The coadministration of buspirone and benzodiazepines may be effective in the treatment of persons with anxiety disorders who have not responded to treatment with either drug alone. R eferences Appelberg BG, Syvalahti EK, Koskinen TE, Mehtonen OP, Muhonen TT, Nauk- karinen HH. Patients with severe depression may benefit from buspirone augmentation of selective serotonin reuptake inhibitors: Results from a pla- cebo-controlled, randomized, double-blind, placebo wash-in study. J Clin Psy- chiatry. 2001;62:448. Benyamina A, Lecacheux M, Blecha L, Reynaud M, Lukasiewcz M. Pharmaco- therapy and psychotherapy in cannabis withdrawal and dependence. Expert Rev Neurother. 2008;8:479. Faber J, Sansone RA. Buspirone: A possible cause of alopecia. Innov Clin Neuro- sci. 2013;10(1):12–13. Le Foll B, Boileau I. Repurposing buspirone for drug addiction treatment. Int J Neuropsychopharmacol. 2013;16(2):251–253. Levitt AJ, Schaffer A, Lanctôt KL. Buspirone. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Vol. 2. Philadelphia: Lippincott Williams & Wilkins: 2009:3060. Myers RA, Plym MJ, Signor LJ, Lodge NJ. 1-(2-pyrimidinyl)-piperazine, a buspi- rone metabolite, modulates bladder function in the anesthetized rat. Neurourol Urodyn. 2004;23(7):709. Navines R, Martin-Santos R, Gomez-Gil E, Martinez De Osaba MJ, Gasto C. Interaction between serotonin 5-Htla receptors and beta-endorphins modu- lates antidepressant response. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1804. SempereT, Urbina M, Lima L. 5-HT1A and beta-adrenergic receptors regulate pro- liferation of rat blood lymphocytes. Neuroimmunomodulation. 2004;11(5):307. Syvalahti E, Penttila J, Majasuo H, Palvimaki EP, Laakso A. Combined treatment with citalopram and buspirone: Effects on serotonin 5-HT 2A and 5-HT 2C recep- tors in the rat brain. Pharmacopsychiatry. 2006;39(1):1. Van Oudenhove L, Kindt S, Vos R, Coulie B, Tack J. Influence of buspirone on gastric sensorimotor function in man. Aliment Pharmacol Ther. 2008;28:1326. Wong H, Dockens RC, Pajor L, Yeola S, Grace JE Jr. 6-Hydroxybuspirone is a major active metabolite of buspirone: Assessment of pharmacokinetics and 5-hydroxytryptamine 1A receptor occupancy in rats. Drug Metab Dispos. 2007; 35(8):1387. The intracellular calcium ion regulates activity of multiple neu- rotransmitters such as serotonin and dopamine, and that action may account for its role as a treatment in mood disorders. Cal- cium channel inhibitors are used in psychiatry as antimanic agents for persons who are refractory to or cannot tolerate treat- ment with first-line mood-stabilizing agents such as lithium (Eskalith), carbamazepine (Tegretol), and divalproex (Depak- ote). Calcium channel inhibitors include nifedipine (Procardia, Adalat), nimodipine (Nimotop), isradipine (DynaCirc), amlo- dipine (Norvasc, Lotrel), nicardipine (Cardene), nisoldipine (Sular), nitrendipine, and verapamil (Calan). They are used for control of mania and ultradian bipolar disorder (mood cycling in less than 24 hours). The results of a large genetic study have rekindled interest in the potential clinical uses of calcium channel blockers (CCBs). Two genome-wide findings implicated genes encoding L-type voltage-gated calcium channel subunits as susceptibility genes for bipolar disorder, schizophrenia, major depressive disorder, ADHD, and autism. ▲▲ 29.12 Calcium Channel Blockers