What it's for (Indications)
- Management of schizophrenia and other psychotic disorders, including acute treatment of agitation associated with schizophrenia.
- Also indicated for acute treatment of manic/mixed episodes of bipolar I disorder and for maintenance treatment of bipolar I disorder as an adjunct to lithium or valproate, and for maintenance of clinical improvement in general.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Oral capsules must be administered with food; do not open, crush, or chew. For schizophrenia: Initiate at 20 mg twice daily. Daily dosage may be adjusted up to 80 mg twice daily, with adjustments occurring at intervals of not less than 2 days. Doses up to 100 mg twice daily have demonstrated safety and efficacy. The lowest effective dose should be used. For acute treatment of manic/mixed episodes of bipolar I disorder: Initiate at 40 mg twice daily. Increase to 60 mg or 80 mg twice daily on Day 2 of treatment. Subsequent dose adjustments should be based on tolerability and efficacy within the range of 40-80 mg twice daily. For maintenance treatment of bipolar I disorder (as an adjunct to lithium or valproate): Continue treatment at the same dose on which the patient was initially stabilized, within the range of 40-80 mg twice daily. For acute treatment of agitation associated with schizophrenia, 10 mg intramuscularly may be administered. |
Safety & Warnings
Common Side Effects
- Common side effects may include asthenia (abnormal weakness), headache, gastrointestinal disturbances, drowsiness, agitation, akathisia (restlessness and urge to move), dizziness, dystonia (abnormal muscle tone), extra-pyramidal syndrome, hypotonia (abnormally low muscle tone), tremor, and abnormal vision.
Serious Warnings
- Black Box Warning: Increased Mortality in Elderly Patients with Dementia-Related Psychosis. Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Ziprasidone is not approved for the treatment of patients with dementia-related psychosis.
- Caution is advised in patients with QT prolongation, neuroleptic malignant syndrome (NMS), tardive dyskinesia, metabolic changes (including hyperglycemia), seizures, and with concomitant use of CNS drugs/alcohol.
- Other severe adverse reactions include increased mortality in elderly patients with dementia-related psychosis, cerebrovascular adverse reactions (including stroke) in elderly patients with dementia-related psychosis, QT prolongation and risk of sudden death, serotonin syndrome, severe cutaneous adverse reactions, rash, orthostatic hypotension, and falls.
- For pregnancy, the risk cannot be ruled out; consult a physician for advice.
- For lactation, this drug is contraindicated or not recommended; consult a physician for advice.
How it Works (Mechanism of Action)
Ziprasidone, an atypical antipsychotic belonging to the benzisothiazolylpiperazine class, exerts its complex therapeutic actions primarily through a multifaceted modulation of central nervous system receptors. Its principal mechanism involves potent antagonism at postsynaptic dopamine D2 receptors, a common pathway for antipsychotic efficacy, particularly in ameliorating positive symptoms of psychosis. Concurrently, ziprasidone demonstrates high affinity and antagonism at serotonin 5-HT2A receptors. This dual D2/5-HT2A antagonism is believed to contribute to its atypical profile, leading to a reduced propensity for extrapyramidal side effects compared to first-generation antipsychotics, while also potentially improving negative and cognitive symptoms. Beyond these primary actions, ziprasidone functions as a partial agonist at serotonin 5-HT1A receptors, a mechanism hypothesized to contribute to its anxiolytic, antidepressant, and cognitive-enhancing properties. It also acts as an antagonist at 5-HT1D receptors. Furthermore, ziprasidone exhibits moderate affinity for histamine H1 receptors and alpha-1 adrenergic receptors, which can account for some observed side effects such as sedation and orthostatic hypotension, respectively. A distinct pharmacological characteristic of ziprasidone is its inhibition of the reuptake of both norepinephrine and serotonin by binding to norepinephrine transporters (NET) and serotonin transporters (SERT), contributing to its antidepressant effects and broader mood stabilization. Notably, ziprasidone possesses negligible affinity for muscarinic M1 cholinergic receptors, thereby minimizing the risk of anticholinergic side effects.