Depressants Chlorpromazine

Krnjevic and Videk ) described a new screening test based on a "natural reaction of a rat, namely the entrance into a darkened cage through a hole of suitable size (5 cm. ). Either of several depressants, chlorpromazine, reserpine, phenobarbital, etc. increased the time required for this reaction. A pyschostimulant, amphetamine, decreased the time, as did the anti-depressants imipramine or nialamide. 

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... 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

In psychiatric practice, chlorpromazine is used in various conditions of psychomotor excitement in patients with schizophrenia, chronic paranoid and also manic-depressive conditions, neurosis, alcohol psychosis and neurosis accompanied by excitement, fear, stress, and insomnia, hi comparison with other neuroleptics, chlorpromazine is unique in that it has an expressed sedative effect. It is sometimes used in anesthesiological practice for potentiating narcosis. It also has moderate anticonvulsant action. The most common synonyms are aminazine, megaphen, largactil, thorazine, prompar, and others. 

Morphine and other opioids exhibit intense sedative effects and increased respiratory depression when combined with other sedatives, such as alcohol or barbiturates. Increased sedation and toxicity are observed when morphine is administered in combination with the psychotropic drugs, such as chlorpromazine and monoamine oxidase inhibitors, or the anxiolytics, such as diazepam. 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

Despite this favorable result, lithium was hardly considered as a psychopharmaceutical for many years. There were a variety of reasons for this. Firstly, mania is not a very common psychosis and there is spontaneous remission in many cases. There were thus not so many occasions where lithium treatment was indicated. Secondly, lithium salts were considered to be toxic because for some time they had been given in excessive doses to patients with heart failure and in this way, had led to a number of fatalities (Cade, 1970). Thirdly, a few years after Cade s first publication psychiatrists attention had been claimed by chlorpromazine and the subsequent neuroleptics and antidepressants, thus explaining why lithium almost fell into oblivion. It was onl> in the 1960s that it once more attracted some interest, after the Danish psychiatrist Mogens Schou had shown that lithium salts were not only useful in the manic phase of manic depressive illness but also could prevent depressive episodes in patients suffering from bipolar psychoses. 

Action on CTZ Chlorpromazine depresses the chemoreceptor trigger zone (CTZ) and acts as a powerful antiemetic agent. 

Treatment Implications. A review of response rates found that only 35% of patients with psychotic depression responded to treatment with a tricyclic antidepressant alone versus 67% of patients with nonpsychotic depression (Table 6-6) (13). Yet these patients have a better response to electroconvulsive therapy (ECT) (14). These patients have also been found to respond to combined treatment with an antidepresssant and an antipsychotic in comparison with either an antidepressant or antipsychotic alone (15). Despite these data, one study found that less than 50% of patients with psychotic depression referred to an ECT service had been treated with an antipsychotic and only 15% had received a daily dose equivalent to 200 mg or more or chlorpromazine ( 16). 

Klein DF. Chlorpromazine-procyclidine combination, imipramine and placebo in depressive disorders. Can Psychiatr Assoc J 1966 11[Suppl 1] 146-149. 

Chlorpromazine has direct effects on the CTZ and may also depress temperature control and prevent shivering. The effects are due to inhibition of dopamine centrally. It may potentiate the effects of hypnotics, sedatives and anaesthetic agents. It is rarely used in anaesthetic practice today. Promethazine was first developed for its antihistamine effects but is more commonly used for its sedative/anticholinergic, anti-emetic actions, and prevention of motion-related sickness. The sedative actions are quite marked and last longer than the anti-emetic effects. 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

The positive effects of the monoamine oxidase inhibitor isoniazid and the amine reuptake blocker imipramine were both discovered by accident. Isoniazid was being used as an antitubercular drug when patients reports of elation led Nathan Kline to test and to demonstrate its antidepressant power. Ronald Kuhn had synthesized imipramine, a tricyclic molecule, as a possible me-too analog of chlorpromazine. When Kuhn found that it had little or no antipsychotic potential, he tried it out on depressives, and voila They got better. After a while, that is. As with isoniazid, imip-ramine s antidepressant action was evident only after one to four weeks of administration. 

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