Introduction
Disorders such as schizophrenia and bipolar disorder can significantly impair mood, cognition, and behavior. These mental illnesses can often be accompanied by comorbidities such as depression and substance abuse, and can significantly impact the quality of life of patients and caregivers. Luckily, several treatment options for psychotic disorders have been introduced to market since the realization of chlorpromazine's antipsychotic properties in 1952.
Second generation antipsychotics (commonly referred to as atypical antipsychotics) include clozapine, quetiapine, olanzapine, aripiprazole and ziprasidone among others, and are generally thought to be as efficacious as first generation antipsychotics but differ in their adverse effect profiles. First generation antipsychotics are associated with extrapyramidal adverse effects while atypical antipsychotics are linked to weight gain, impaired glucose tolerance and metabolic syndrome.
Zipradon Capsule 40 mg is used to treat schizophrenia and bipolar disorder. It can effectively reduce the rate and time of relapses in schizophrenia, and can be used to treat manic episodes in bipolar disorder although the mechanism of action is unknown. Although ziprasidone is classified as an atypical antipsychotic, it appears to have a lower incidence of metabolic adverse effects compared to other medications in the same class.
Uses
Zipradon Capsule 40 mg is an atypical antipsychotic used to manage schizophrenia, bipolar mania, and agitation in patients with schizophrenia.
In its oral form, ziprasidone is approved for the treatment of schizophrenia, as monotherapy for acute treatment of manic or mixed episodes related to bipolar I disorder, and as adjunctive therapy to lithium or valproate for maintenance treatment of bipolar I disorder. The injectable formulation is approved only for treatment of acute agitation in schizophrenia.
Associated Conditions
Pharmacodynamics
Zipradon Capsule 40 mg is classified as a "second generation" or "atypical" antipsychotic and is a dopamine and 5HT2A receptor antagonist with a unique receptor binding profile. As previously mentioned, ziprasidone has a very high 5-HT2A/D2 affinity ratio, binds to multiple serotonin receptors in addition to 5-HT2A, and blocks monoamine transporters which prevents 5HT and NE reuptake. On the other hand, ziprasidone has a low affinity for muscarinic cholinergic M1, histamine H1, and alpha1-adrenergic receptors.
Mechanism of Action
The effects of ziprasidone are differentiated from other antispychotics based on its preference and affinity for certain receptors. Zipradon Capsule 40 mg binds to serotonin-2A (5-HT2A) and dopamine D2 receptors in a similar fashion to other atypical antipsychotics; however, one key difference is that ziprasidone has a higher 5-HT2A/D2 receptor affinity ratio when compared to other antipsychotics such as olanzapine, quetiapine, risperidone, and aripiprazole. Zipradon Capsule 40 mg offers enhanced modulation of mood, notable negative symptom relief, overall cognitive improvement and reduced motor dysfunction which is linked to it's potent interaction with 5-HT2C, 5-HT1D, and 5-HT1A receptors in brain tissue. Zipradon Capsule 40 mg can bind moderately to norepinephrine and serotonin reuptake sites which may contribute to its antidepressant and anxiolytic activity. Patient's taking ziprasidone will likely experience a lower incidence of orthostatic hypotension, cognitive disturbance, sedation, weight gain, and disruption in prolactin levels since ziprasidone has a lower affinity for histamine H1, muscarinic M1, and alpha1-adrenoceptors.
Absorption
In the absence of food, ziprasidone's oral bioavailability is 60%, and absorption may reach 100% if ziprasidone is taken with a meal containing at least 500 kcal. The difference in bioavailability has little to do with the fat content of the food and appears to be related to the bulk of the meal since more absorption occurs the longer ziprasidone remains in the stomach.
Volume of Distribution
The mean apparent volume of distribution of Zipradon Capsule 40 mg is 1.5 L/kg.
Protein Binding
Zipradon Capsule 40 mg is extensively protein bound with over 99% of the drug bound to plasma proteins, primarily albumin and alpha1-acid glycoprotein.
Route of Elimination
Zipradon Capsule 40 mg is extensively metabolized after oral administration with only a small amount excreted in the urine (<1%) or feces (<4%) as unchanged drug.
Half Life
The half life of ziprasidone is 6-7 hours.
Clearance
The mean apparent systemic clearance is 7.5 mL/min/kg.
Toxicity
The most common adverse reactions reported with ziprasidone include somnolence, respiratory tract infections, extrapyramidal symptoms, dizziness, akathisia, abnormal vision, asthenia, vomiting, headache and nausea.
Food Interactions
- Avoid alcohol.
- Take with food.
Dosage
Schizophrenia: Initiate at 20 mg twice daily. Daily dosage may be adjusted up to 80 mg twice daily. Dose adjustments should occur at intervals of not less than 2 days. Safety and efficacy has been demonstrated in doses up to 100 mg twice daily. The lowest effective dose should be used.
Acute treatment of manic/mixed episodes of bipolar I disorders: 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.
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.
Acute treatment of agitation associated with schizophrenia (intramuscular administration): 10 mg 20 mg up to a maximum dose of 40 mg per day. Doses of 10 mg may be administered every 2 hours. Doses of 20 mg may be administered every 4 hours.
