Extrapyramidal effects aripiprazole

The term neuroleptic is often applied to drngs that have relatively prominent experimental and clinical evidence of antagonism of D2-dopamine-receptor activity, with substantial risk of adverse extrapyramidal nenrological effects and inaeased release of prolactin. The term atypical antipsychotic is applied to agents that are associated with snbstantially lower risks of snch extrapyramidal effects. Representative examples inclnde aripiprazole, clozapine, quetiapine, ziprasidone, and low doses of olanzapine and risperidone. 

Adverse Neurological Effects Many neurological syndromes, particularly involving the extrapyramidal motor system, occur following the use of most antipsychotic drugs, especially with the high-potency D -receptor antagonists (tricyclic piperazines and butyrophenones). Acute adverse extrapyramidal effects are less likely with aripiprazole, clozapine, quetiapine, thioridazine, and ziprasidone, or low doses of olanzapine or risperidone. 

Extrapyramidal side-effects generally appear with blockade of dopamine D2 receptors in excess of 80%, whereas clinical efficacy in treating psychosis is associated with 60-70% D2 receptor blockade [12]. Recently, a partial agonist for the D2 receptor known as aripiprazole has been developed, which results in approximately 70% antagonism/30% agonism at the D2 receptor. It is an effective antipsychotic, has low risk for extrapyramidal symptoms, and does not cause elevated levels of prolactin as do the full antagonists at D2 receptors. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Effects, below. Newer antipsychotics such as olanzapine, quetiapine, and aripiprazole cause no or minimal increases of prolactin and reduced risks of extrapyramidal system dysfunction and tardive dyskinesia, reflecting their diminished D2 antagonism. 

ARIPIPRAZOLE, HALOPERIDOL, CLOZAPINE, PIMOZIDE, RISPERIDONE, SERTINDOLE PROTEASE INHIBITORS Possibly T levels of antipsychotic Inhibition of CYP3A4- and/or CYP2D6-mediated metabolism Avoid co-administration of clozapine with ritonavir, and pimozide or sertindole with protease inhibitors. Use other antipsychotics with caution as 1 dose may be required with risperidone, watch closely for extrapyramidal side-effects and neuroepileptic malignant syndrome... 

Atypical antipsychotics such as aripiprazole, olanzapine, que-tiapine, risperidone, and ziprasidone are effective as monotherapy or adjunctive therapy with lithium and valproate in the treatment of acute mania. Some antipsychotics have the potential to cause adverse effects such as extrapyramidal reactions, sedation, depression, emotional blunting, sexual dysfunction, weight gain, and orthostatic hypotension. Prophylactic use of antipsychotics may be needed for some patients with recurrent mania or mixed states, but the risks versus benefits must be weighed because of long-term adverse effects (e.g., obesity, type 2 diabetes, hyperlipidemia, hyperprolactinemia, cardiac disease, and tardive dyskinesia). ... 

Quetiapine has sedative effects and may cause weight gain, bnt it causes minimal extrapyramidal side effects or prolactin elevations. Ziprasidone canses few extrapyramidal side effects, does not significantly increase prolactin levels, and has a lower risk of causing weight gain. Aripiprazole has low extrapyramidal side effects (except for initial akathisia), minimal effect on prolactin levels, and is considered to be weight neutral. 

Fluoxetine and probably paroxetine may cause clinically significant increases in aripiprazole levels. The concurrent use of aripiprazole with SSRIs or venlafaxine has led to adverse effects such as the neuroleptic malignant syndrome and extrapyramidal symptoms. 

The concurrent use of aripiprazole and SSRIs can be useful, but it is important to remember to adjust the dose if paroxetine or fluoxetine are started or stopped, and be aware that, rarely, adverse effects such as extrapyramidal symptoms and the neuroleptic malignant syndrome may develop. 

Cohen ST, Rulf D, PiesR. Extrapyramidal side effects associated widi aripiprazole coprescription in 2 patients. J Clin Psychiatry (2005) 66, 135-6. 

In a 12-week, multicenter, randomized, double-blind, placebo-controlled trial of aripiprazole in the treatment of alcoholism in 295 subjects, aripiprazole produced more positive subjective effects and less overall severity of alcohol dependence than placebo, although there was no difference between aripiprazole and placebo on the primary end-point, possibly because of dose-related attrition (treatment was started at 2 mg/day and titrated to a maximum of 30 mg/day at day 28). Withdrawals (40% versus 27%) and treatment-related adverse effects (83% versus 64%) were more common with aripiprazole. The most common treatment-related adverse events that differed significantly between aripiprazole and placebo were fatigue, insomnia, restlessness, somnolence, anxiety, and altered attention serious adverse reactions attributed to aripiprazole were chest pain, cellulitis, migraine, and thrombosis extrapyramidal adverse reactions attributed... 

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