Lithium antipsychotic drugs

List the major receptors blocked by antipsychotic drugs. 

Describe the pharmacodynamics of older antipsychotic drugs and relate these characteristics to their clinical uses. 

Identify the main characteristics and clinical uses of newer atypical antipsychotic drugs. 

List the major adverse effects of the antipsychotic dmgs. 

The antipsychotic drugs (neuroleptics) are effective in controlling many manifestations of psychotic illness. Though the disease is not cured by drug therapy, the symptoms of sehizophrenia, ineluding thought disorder, emotional withdrawal, and hallucinations or delusions, may be attenuated by antipsychotic drugs. Unfortunately, protracted therapy (years) is often needed and ean result in severe toxicity in some patients. 

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Lithium was the first agent shown to be useful in the treatment of the manic phase of bipolar disorder that was not also an antipsychotic drug. Lithium... 

Although lithium is not a true antipsychotic drug, it is considered with the antipsychotics because of its use in regulating the severe fluctuations of the manic phase of bipolar disorder (a psychiatric disorder characterized by severe mood swings of extreme hyperactivity to depression). During the manic phase, the person experiences altered thought processes, which can lead to bizarre delusions. The drug diminishes the frequency and intensity of hyperactive (manic) episodes. 

It is common for lithium to be combined with other mood-stabilizing drugs or antipsychotic drugs, if necessary, in order to achieve more complete remission of symptoms. Studies indicate that monotherapy is often insufficient to reach this goal.17... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Introduced in clinical practice in the 1960s, lithium was the first mood stabilizer to be used in China. This was followed by carbamazepine and sodium valproate. For many years, these were the only treatment options available as mood stabilizers. Although lamotrigine was approved for maintenance treatment of bipolar I disorder in 2003 by FDA (Food and Drug Administration) in the USA, this indication has not yet been approved by the Chinese authorities. At present, only one atypical antipsychotic drug, risperidone, has been approved for treating acute mania (February 2005 by SFDA [State Food and Drug Administration]) in China (see Table 6.1). 

It is common for both the depressive and manic phases to occur simultaneously in what is termed a mixed state or dysphoric mania. During these mixed episodes, the patient s mood is characterized by symptoms of both a depression and mania. Mixed episodes often have a poorer outcome than classic euphoric mania and, as a rule, respond better to certain anticonvulsants and atypical antipsychotic drugs than to lithium. As many as 50% of admissions to inpatient psychiatric facilities for the treatment of manic episodes appear to be for mixed manic states. The recognition... 

Lithium remains the treatment of choice for bipolar patients who experience classic euphoric episodes of mania. Current evidence suggests that those with mixed episodes or rapid cycling episodes respond preferably to anticonvulsants or atypical antipsychotic drugs. In addition to its use as a mood stabilizer, lithium is effective in converting unipolar antidepressant nonresponders to responders. Finally, lithium may also be an effective treatment for patients with clnster headaches. 

Antipsychotic drugs, such as flupentixol and haloperidol are the mainstay of treatment for acute attacks of mania. Lithium is not indicated as it may take a few days before the drug exerts an effect. Lithium may be given concomitantly with an antipsychotic drug. 

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. 

Schizoaffective disorder, another condition with an affective component characterized by a mixture of schizophrenic symptoms and depression or excitement, is treated with antipsychotic drugs alone or combined with lithium. Various antidepressants are added if depression is present. 

Lithium alone is rarely successful in treating schizophrenia, but adding it to an antipsychotic may salvage an otherwise treatment-resistant patient. Carbamazepine may work equally well when added to an antipsychotic drug. 

Serum prolactin concentrations in patients taking longterm (n = 15) or short-term (n = 15) lithium did not differ from controls (613). In another study, when compared with 17 healthy controls, 20 euthymic bipolar patients who had taken lithium for more than 6 months had significantly lower serum prolactin concentrations (9.72 ng/ ml versus 15.56 ng/ml), but prolactin concentrations in short-term lithium users (n = 15) did not differ from controls (614). Antipsychotic drugs were not involved. 

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