Antipsychotic drugs quetiapine

MandrioU, R. FanaU, S. Ferranti, A. Raggi, M.A. HPLC analysis of the novel antipsychotic drug quetiapine in hmnan plasma, J.Pharm.Biomed.Anal., 2002,30,969-977. [triprolidine is internal standard SPE LOQ 4 ng/mL]... 

Principally because of its efficacy/tolerability ratio, prescriptions for quetiapine are growing faster than for any other atypical antipsychotic drug at present (personal communication, Astra Zeneca). 

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Antiadrenergic drugs (prazosin) can be useful in some patients with PTSD, and antipsychotics (risperidone, quetiapine, and olanzapine) may be used as augmenting agents in partial responders. 

Tardive dyskinesia refers to uncontrollable facial movements. It is more likely to occur in the elderly. Tardive dyskinesia is commonly associated with the use of antipsychotic drugs, such as haloperidol. The atypical antipsychotics, such as clozapine, olanzapine, risperidone and quetiapine are less likely to cause tardive dyskinesia. 

Gl dysmotility Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Use quetiapine, ziprasidone, risperidone, olanzapine, aripiprazole, and others cautiously in patients at risk for aspiration pneumonia. Hypersensitivity reactions Patients who have demonstrated a hypersensitivity reaction (eg, blood dyscrasias, jaundice) with a phenothiazine should not be re-exposed to any phenothiazine unless the potential benefits of treatment outweigh the possible hazards. 

D2 receptor, albeit with different specificity. Older examples of dopamine antagonists are chlorpromazine, haloperidol and many derivatives of these prototype compounds. Newer antipsychotic drugs such as risperidone, olanzapine and quetiapine have retained this mechanism of action, although no longer exclusively. 

Most antipsychotic drugs cause unpleasant subjective effects in nonpsychotic individuals. The mild to severe EPS, including akathisia, sleepiness, restlessness, and autonomic effects are unlike any associated with more familiar sedatives or hypnotics. Nevertheless, low doses of some of these drugs, particularly quetiapine, are used to promote sleep onset and maintenance, although there is no approved indication for such usage. 

Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. They are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid. The manic phase in bipolar affective disorder often requires treatment with antipsychotic agents, although lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics in the acute phase (up to 4 weeks) of mania, and olanzapine and quetiapine has been approved for this indication. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

Hyperlipidemia associated with antipsychotic drugs has been reviewed (SEDA-29, 64). Haloperidol and the atypical antipsychotic drugs ziprasidone, risperidone, and aripiprazole would be associated with lower risks of hyperlipidemia, whereas chlorpromazine, thioridazine, and the atypical drugs quetiapine, olanzapine, and clozapine would be associated with higher risks. However, severe clozapine-induced hypercholesterolemia and hypertriglyceridemia has been reported in a patient taking clozapine (55). 

Seeman P, Tallerico T (1999) Rapid release of antipsychotic drugs from dopamine d2 receptors An explanation for low receptor occupancy and early clinical relapse upon withdrawal of clozapine or quetiapine. Am J Psychiatry 156(6) 876-884... 

The discovery of the atypical antipsychotic clozapine opened a new era and set new standards in the drug treatment of schizophrenia. Modifications of the diben-zoazepine structure in clozapine resulted in olanzapine and quetiapine, which are among the most frequently used antipsychotic drugs. From a chemical viewpoint, clozapine, olanzapine and quetiapine can be considered as structural analogues. Although they share some common features in their molecular mechanism of action, the three compounds show significant differences in their clinical efficacy and adverse event profile. 

Data from short-term clinical trials (6 weeks) suggest that quetiapine may be useful for the management of psychotic disorders in patients who do not tolerate the adverse effects of the typical antipsychotic drugs or clozapine (3). The most common adverse effects of quetiapine were dizziness, hypotension, somnolence, and weight gain. Raised hepatic enzymes have also been reported. In addition, two patients with idiopathic Parkinson s disease and psychosis were treated with quetiapine for 52 weeks (4). Psychotic symptoms were successfully controlled without worsening of motor disability. 

Two patients with schizophrenia who developed focal tardive dystonia with atypical antipsychotic drugs (risperidone and olanzapine) had marked sustained improvement when quetiapine was gradually introduced and the other antipsychotic drugs were withdrawn there was no loss of control of psychotic symptoms (10). 

Among the atypical antipsychotic drugs available in Europe, quetiapine seems to be associated with less... 

Goldstein JM. Quetiapine fumarate (Seroquel) a new atypical antipsychotic. Drugs Today (Bare) 1999 35(3) 193-210. 

Responders to drug therapy should continue treatment for at least 12 months. When discontinued, drug therapy should be tapered slowly over a period of 1 month or more to reduce the likelihood of relapse. Antiadrenergic drugs (prazosin) can be useful in some patients with PTSD, and antipsychotics (risperidone, quetiapine, and olanzapine) may be used as augmenting agents in partial responders. 

Examples of plasma half-lives for antipsychotics include quetiapine 7 h, clozapine 12 h, haloperidol 18 h and olazapine 33 h. Depot intramuscular injections are available from which drug is released over 2-4 weeks. 

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