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29.29 Serotonin–Dopamine Antagonists and Similarly Acting Drugs (Second-Generation or Atypical Antipsychotics)

phenytoin) increasing its dose should be considered. This is especially important when a strong CYP inducer is coadmin- istered for greater than 14 days. The maximum recommended dose should not exceed three times the original dose. The dose of vortioxetine should be reduced to the original level within 14 days, when the inducer is discontinued. Although vortioxetine can be abruptly discontinued, in placebo-controlled trials patients experienced transient adverse reactions such as headache and muscle tension following abrupt discontinuation of vortioxetine 15 mg/day or 20 mg/day. To avoid these adverse reactions, it is recommended that the dose be decreased to 10 mg/day for one week before full discontinu- ation of vortioxetine 15 mg/day or 20 mg/day Vortioxetine is available in 5 milligram (mg), 10 mg, 15 mg and 20 mg tablets. R eferences Ashton AK, Longdon MC. SSNRI-induced, dose dependent, nonmenstrual, vagi- nal spotting and galactorrhea accompanied by prolactin elevation (Letter). Am J Psychiatry. 2007;164:1121. Baldessarini RJ, Pompili M, Tondo L. Suicidal risk in antidepressant drug trials. Arch Gen Psychiatry. 2006;63:246. Barbui C, Esposito E, Cipriani A. Selective serotonin reuptake inhibitors and risk of suicide: A systematic review of observational studies. CMAJ. 2009;180:291. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med. 2006;354:579. Cipriani A, Barbui C, Brambilla P, Furukawa TA, Hotopf M. Are all antidepres- sants really the same? The case of fluoxetine: A systematic review. J Clin Psy- chiatry. 2006;67:850. Cipriani A, Furukawa TA, Salanti G, Geddes JR, Higgins JPT. Comparative efficacy and acceptability of 12 new-generation antidepressants: A multiple-treatments meta-analysis. Lancet. 2009;373:746. Clayton A, Kornstein S, Prakash A, Mallinckrodt C, Wohlreich M. Changes in sexual functioning associated with duloxetine, escitalopram, and pla- cebo in the treatment of patients with major depressive disorder. J Sex Med. 2007;4:917. Cohen LS, Altshuler LL, Harlow BL, Nonacs R, Newport DJ. Relapse of major depression during pregnancy in women who maintain or discontinue antide- pressant treatment. JAMA. 2006;295:499. Couturier J, Sy A, Johnson N, Findlay S. Bone mineral density in adolescents with eating disorders exposed to selective serotonin reuptake inhibitors. Eat Disord. 2013;21(3):238. Cowen P, Sherwood AC. The role of serotonin in cognitive function: Evidence from recent studies and implications for understanding depression. J Psycho- pharmacol. 2013;27(7):575. Diem SJ, Blackwell TL, Stone KL,Yaffe K, Haney EM. Use of antidepressants and rates of hip bone loss in older women: The study of osteoporotic fractures. Arch Intern Med. 2007;167:1240. Glassman AH, O’Connor CM, Califf RM, Swedberg K, Schwartz P. Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men. Arch Intern Med. 2007;167(12):1246. Hu X-Z, Rush AJ, Charney D, Wilson AF, Sorant AJM. Association between a functional serotonin transporter promoter polymorphism and citalopram treatment in adult outpatients with major depression. Arch Gen Psychiatry. 2007;64:783. Looper KL. Potential medical and surgical complications of serotonergic antide- pressant medications. Psychosomatics. 2007;48:1. Nurnberg GH, Hensley PL, Heiman JR, Croft HA, Debattista C. Sildenafil treat- ment of women with antidepressant-associated sexual dysfunction: A random- ized controlled trial. JAMA. 2008;300:395. Sussman N. Selective serotonin reuptake inhibitors. In: Sadock BJ, Sadock VA, Ruiz P, eds. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9 th ed. Vol. 2. Philadelphia: Lippincott Williams & Wilkins; 2009:3190. Thase ME, Haight BR, Richard N, Rockett CB, Mitton M. Remission rates fol- lowing antidepressant therapy with bupropion or selective reuptake inhibitors: A meta-analysis of original data from 7 randomized controlled trials. J Clin Psychiatry. 2005;66:974. Trivedi MH, Rush AJ, Wisniewski SR, Nierenberg AA, Warden D, STAR*D Study Team. Evaluation of outcomes with citalopram for depression using measure- ment-based care in STAR*D: Implications for clinical practice. Am J Psychia- try. 2006;163:28. Weissman AM, Levy BT, Hartz, AJ, Bentler S, Donohue M. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066.

▲▲ 29.29 Serotonin– Dopamine Antagonists and Similarly Acting Drugs (Second-Generation or Atypical Antipsychotics)

The serotonin–dopamine antagonists (SDAs), also known as second-generation or atypical antipsychotic drugs, are a group of pharmacologically diverse drugs that have largely supplanted the older dopamine receptor antagonists (DRAs). The term atypical is used because these drugs differ in their side effect profiles, most notably a lower risk of extrapyramidal side effects (EPS), and have spectra of action that are broader than those of the DRAs. In contrast to the earlier antipsychotic drugs, the SDAs have significant effects on both the dopamine and sero- tonin systems. Their pharmacology is complex, with individual drugs in this group having multiple neurotransmitter effects. All SDAs are indicated for the treatment of schizophrenia. Most of these second-generation antipsychotic drugs have also received approval as monotherapy or adjunctive therapy in the treatment of bipolar disorder. Some have also been approved as adjuncts for treatment of major depression. As of 2013, ten second-generation antipsychotic drugs were approved by the Food and Drug Administration (FDA). These include the following: risperidone (Risperdal), risperidone IM long acting (Consta), olanzapine (Zyprexa), olanzapine for extended-release injectable suspension (Zyprexa, Relprevv), quetiapine (Seroquel), quetiapine XR (Seroquel XR), ziprasi- done (Geodon), aripiprazole (Abilify), paliperidone (Invega), paliperidone palmitate (Invega, Invega Sustenna), asenapine (Saphris), lurasidone (Latuda), iloperidone (Fanapt), and clo- zapine (Clozaril). It is arguable whether the SDAs represent an improvement in overall tolerability than the DRAs. Although there is improve- ment with respect to a lowered, but not absent, risk of EPS, most of the drugs in this group often produce substantial weight gain, which in turn increases the potential for development of dia- betes mellitus. Olanzapine and clozapine appear to account for most cases of weight gain and drug-induced diabetes mellitus. The other agents pose a smaller risk of these side effects; nev- ertheless, the FDA has requested that all SDAs carry a warning label that patients taking the drugs be monitored closely, and has recommended the following factors be considered for all patients prescribed second-generation antipsychotics. 1. Personal and family history of obesity, diabetes, dyslipid- emia, hypertension, and cardiovascular disease 2. Weight and height (so that body mass index can be calcu- lated) 3. Waist circumference (at the level of the umbilicus) 4. Blood pressure 5. Fasting plasma glucose level 6. Fasting lipid profile Patients with preexisting diabetes should have regular moni- toring, including hemoglobin A1C (HgA1C) and in some cases insulin levels. Among these drugs, clozapine sits apart. It is not