Atypical antipsychotics adverse effects

Sprinkle capsule 15, 25 mg Atypical Antipsychotics FDA approved for use in bipolar disorder Aripiprazole Abilify Tablets 5, 10, 15, Dosage should be slowly increased to minimize adverse effects (e.g., 25 mg at bedtime for 1 week, then 25-50 mg/day increments at weekly intervals) 10-30 mg/day once daily acute treatment of mania or mixed episodes due to lack of efficacy used as an adjunctive agent with established mood stabilizers Use as monotherapy or in... 

Clozapine and olanzapine are atypical antipsychotic drugs used in the treatment of schizophrenia. Their strnctnres are depicted in Scheme 2.36. The use of clozapine and olanzapine, which are more effective than standard neuroleptic drugs in the treatment of refractory schizophrenia, is, however, limited becanse of their adverse effects. These adverse effects are ascribed to the formation of the corresponding cation-radicals in living organisms under oxidation by bone marrow cells. These cation-radicals eliminate protons from the NH fragments and generate their nitrenium cations. The nitreninm cations are covalently bonnd to the life-important proteins. This results in the toxic effects of clozapine and olanzapine (Sikora et al. 2007). 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

Haddad PM, Sharma SG. Adverse effects of atypical antipsychotics differential risk and clinical implications. CNS Drugs 2007 21(ll) 911-36. 

All clinically effective antipsychotics block DA receptor activity. Further, stimulation of this neurotransmitter can induce psychotic symptoms de novo or exacerbate an existing psychotic disorder. Atypical agents have differential impacts on other systems (e.g., 5-HT) in comparison with the earlier neuroleptic agents. They also selectively target specific DA tracts that may mediate the pathological condition, while sparing those tracts that mediate the unwanted adverse effects (e.g., EPS, TD). 

Sedation, ataxia, and cognitive impairment occur more frequently with high BZD dosages. Other adverse effects reported when BZDs were used to treat schizophrenia include behavioral disinhibition, exacerbation of psychosis, and increase in anxiety and depression ( 163, 188, 189,190, 191,192, 193,194 and 195, 351). Concomitant use of a BZD and the atypical antipsychotic clozapine may increase the risk of sedation, dizziness and collapse with loss of consciousness ( 196). Respiratory compromise has also been reported with this combination (395, 396). 

During 2004 a number of clinical trials were reported involving acute and maintenance studies of lithium, mostly either comparing new atypical antipsychotic drugs with lithium in bipolar disorder or in combined treatment studies. Of the relatively few studies of the adverse effects of lithium, most clustered in the areas of cardiovascular effects and issues regarding lithium toxicity. 

The adverse effects of lithium in elderly patients include cognitive status worsening, tremor, and hypothyroidism. The authors suggested that divalproex is also useful in elderly patients with mania and that concentrations of divalproex in the elderly are similar to those useful for the treatment of mania in younger patients. They noted that carbamazepine should be considered a second-line treatment for mania in the elderly. A partial response would warrant the addition of an atypical antipsychotic drug. For bipolar depression, they recommended lithium in combination with an antidepressant, such as an SSRI. They also noted that lamotrigine may be useful for bipolar depression. Electroconvulsive therapy (ECT) may also be useful, but there have been no comparisons of ECT and pharmacotherapy in elderly patients with bipolar depression. 

Meltzer HY, Casey DE, Garver DL, Lasagna L, Marder SR, Masand PS, Miller D, Pickar D, Tandon R. Adverse effects of the atypical antipsychotics. J Clin Psychiatry 1998 59(Suppl 12) 17-22. 

Schneider LS, Dagerman KS, Insel P. Efficacy and adverse effects of atypical antipsychotics for dementia meta-ana-lysis of randomized, placebo controlled trials. Am J Geriatr Psychiatry 2006 14 191-210. 

Catatonic schizophrenia is a controversial syndrome, and there is debate about its etiology and treatment. There has been a report of two cases of catatonic schizophrenia successfully treated with clozapine a 49-year-old woman and a 19-year-old man (18). Both responded to clozapine despite being resistant to several conventional and atypical antipsychotic drugs and, in the second case, a course of electroconvulsive therapy. These two cases are intriguing, because the dose of clozapine required to improve catatonia was about double the dose required to improve psychosis significantly (600 mg/day and 750 mg/day). The two patients had common adverse effects of clozapine the first had mild nocturnal hypersalivation and mild/moderate constipation, and the second had moderate nocturnal hypersalivation. 

Atypical drugs can provoke a range of adverse effects that is similar to that of the classical antipsychotics but is generally lesser in degree (with exceptions). The following are the main differences. 

---