Ziprasidone adverse effects

In a 28-year-old woman with psychotic symptoms resistant to monotherapy with clozapine or ziprasidone, the combination produced marked improvement in both positive and negative symptoms along with a reduction in adverse effects body weight fell, blood pressure, pulse, and the electrocardiogram remained normal, and valproic acid, which had been introduced for epileptic seizures during clozapine monotherapy, was successfully withdrawn (23). 

Ziprasidone is apparently well tolerated, with a limited potential to cause extrapyramidal adverse effects or weight gain (4). Out-patients who partly respond to conventional antipsychotic drugs, risperidone, or olanzapine may have improved control of psychotic symptoms after switching to ziprasidone, according to the results of a reanalysis of 6-week, multicenter, randomized, open, parallel-group studies in patients with schizophrenia who had previously taken conventional antipsychotic drugs (n = 108), olanzapine (n = 104), or risperidone (n = 58) these results have been published in two different journals (5, 6). 

In an open 12-week study of ziprasidone in 12 patients with Parkinson s disease and psychosis, two withdrew because of adverse effects one had increased diurnal sedation on day 5 and the other had deterioration of gait at 1 week (7C). The other 10 patients reported significant improvement in psychiatric symptoms and no deterioration in motor symptoms. The small sample size and lack of a control group precluded definitive conclusions. 

Ketoconazole caused a modest increase in the mean AUC (33%) and the mean Cmax (34%) of ziprasidone. This effect was not considered clinically relevant and suggests that other inhibitors of CYP3A4 are unlikely to affect the pharmacokinetics of ziprasidone significantly. Most of the reported adverse events were mild. The adverse events that were most commonly reported in subjects who took the drugs concomitantly were dizziness, weakness, and somnolence. There were no treatment-related laboratory abnormalities or abnormal vital signs during the study and at the 6-day follow-up evaluation. 

Infants of women who choose to breast feed while on ziprasidone should be monitored for possible adverse effects... 

Intramuscular ziprasidone has recently been compared with intramuscular haloperidol in the treatment of acute psychosis for a very short period (66). Patients were randomly allocated to intramuscular ziprasidone for up to 3 days of flexible dosing (n = 90 last oral daily dose 91 mg) or haloperidol (n = 42 last oral daily dose 14 mg) followed by oral treatment to day 7. Mean reductions from baseline in all efficacy variables were significantly greater with ziprasidone than with haloperidol at the end of the study. The percentage of patients who had any adverse event was lower with ziprasidone (46%) than with haloperidol (60%) most of the adverse effects were mild or moderate. Four patients discontinued ziprasidone owing to adverse events compared with one in the haloperidol group. 

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). ... 

Phenothiazines, butyrophenones, diphenylbutylpiperidines and thioxanthenes can oppose the effects of levodopa because of their dopamine antagonist properties, causing deterioration of motor function in Parkinson s disease. The antipsychotic effects and ex-trapyramidal adverse effects of these drugs can be opposed by levodopa. Of the atypical antipsychotics, risperidone and olanzapine cause deterioration in motor function in Parkinson s disease. Ziprasidone may act similarly, and there have been reports with quetiapine. Clozapine does not have this effect. 

Of the atypical antipsychotics, both risperidone and olanzapine have caused deterioration of motor function in patients with Parkinson s disease. There have also been reports of deterioration in motor function with quetiapine. There is far less experience with ziprasidone, but it may have a propensity to cause extrapyramidal adverse effects that is similar to olanzapine. 

In a placebo-controlled, crossover study, 18 women taking an oral contraceptive (ethinylestradiol/levonorgestrei 30/150 micrograms) for at least 3 months were also given ziprasidone 20 mg twice daily for 8 days. The only change in the pharmacokinetics of the two steroids was an approximately 30-minute increase in the time to maximum plasma concentration of the levonorgestrel, but this was not considered to be clinically significant. No adverse effects occurred. It was concluded that combined use is safe and that ziprasidone does not affect the efficacy of this oral contraceptive and is also unlikely to affect the metabolism and therefore effieaey of other similar contraceptives. 

Observational studies Numerous open studies of ziprasidone promoted by Pfeer, the marketing authorization holder, have previously been published [SEDA-32, 111] and further studies, similarly promoted, have emerged. Of 185 subjects who were switched from olanzapine or risperidone to ziprasidone, 72 completed a 1-year extension study [136 ]. The most common adverse effects were insomnia (23%) and somnolence (11%) no patient had a corrected QT interval over 500 ms at any time during the study. 

In 70 patients with schizophrenia and persistent symptoms or troublesome adverse effects who were assigned to a flexible dosage (40-160 mg/day) in a 12-month open trial of ziprasidone looking for cognitive improvement, there were significant improvements in executive functions, attention, and information processing domains, but the effect sizes were moderate [138 j. 

In a 4-week, randomised, open-label comparison of ziprasidone and clozapine in the treatment of psychotic symptoms in Parkinson s disease, the most common initial adverse effect was somnolence [47 ]. There was no difference in movement disorder scales between the two antipsychotics. 

In one double-blind, randomized, placebo-controlled study, patients were given a daily dose of 40 or 120 mg ziprasidone or placebo for 28 days in 132 patients ( 136). There was a statistically significant improvement in psychotic symptoms versus placebo in the 120 mg/day ziprasidone group as measured by the total BPRS and the CGI scores. Evaluations for parkinsonian symptoms, akathisia, abnormal movements, and sedation did not reveal any notable treatment effects. No significant differences existed between drug and placebo in the total number of adverse events, laboratory test abnormalities, or more serious adverse events. Thus, this study documented that 60 mg ziprasidone twice daily was an effective strategy with negligible risks. 

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. 

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