Psychosis antipsychotic drugs

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]. 

The typical antipsychotic drugs, which for 50 years have been the mainstay of treatment of schizophrenia, as well as of psychosis that occurs secondary to bipolar disorder and major depressive disorder, affect primarily the positive symptoms[10]. The behavioral symptoms, such as agitation or profound withdrawal, that accompany psychosis, respond to the antipsychotic drugs within a period of hours to days after the initiation of treatment. The cognitive aspects of psychosis, such as the delusions and hallucinations, however, tend to resolve more slowly. In fact, for many patients the hallucinations and delusions may persist but lose their emotional salience and intrusiveness. The positive symptoms tend to wax and wane over time, are exacerbated by stress, and generally become less prominent as the patient becomes older. 

The most common indications for antipsychotic drugs are the treatment of acute psychosis and the maintenance of remission of psychotic symptoms in patients with schizophrenia. More recently, the atypical antipsychotics have become part of the standard repertoire for the treatment of bipolar disorder, as discussed in Chapter 5. Antipsychotic drugs also ameliorate psychotic symptoms associated... 

As with antidepressant therapy, reversal of psychosis is often gradual and may occur over several weeks to several months. Guidelines for the acute use of antipsychotic drugs are summarized in Table 4— 2 usual dosages for each of the commonly used antipsychotic drugs are summarized in Table 4—1. 

The 2004 Practice Guideline for the Treatment of Patients With Schizophrenia recommends indefinite maintenance treatment for patients who have had at least two episodes of psychosis within 5 years or who have had multiple previous episodes (Lehman et al. 2004). Maintenance therapy should involve the lowest possible doses of antipsychotic drugs, and patients should be monitored closely for symptoms of relapse. If the patient is compliant with treatment, oral medications are usually sufficient. However, if the patient s treatment history suggests that the patient may not reliably take daily oral medication, a long-acting depot preparation may be indicated. 

Antipsychotic drugs or major tranquillizers used in all types of psychosis mainly schizophrenia. 

Nonpsychotic persons also experience impaired performance as judged by a number of psychomotor and psychometric tests. Psychotic individuals, however, may actually show improvement in their performance as the psychosis is alleviated. The ability of the atypical antipsychotic drugs to improve some domains of cognition in patients with schizophrenia and bipolar disorder is controversial. Some individuals experience marked improvement and for that reason, cognition should be assessed in all patients with schizophrenia and a trial of an atypical agent considered, even if positive symptoms are well controlled by typical agents. 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

The earliest effective treatments for schizophrenia and other psychotic illnesses arose from serendipitous clinical observations rather than from scientific knowledge of the neurobiological basis of psychosis or the mechanism of action of effective antipsychotic agents. Thus, the fist antipsychotic drugs were discovered by accident in the 1950s when a putative antihistamine (chlorpromazine) was serendipitously observed to have antipsychotic effects when tested in schizophrenic patients. Chlorpromazine indeed has antihistaminic activity, but its therapeutic actions in schizophrenia are not mediated by this property. Once chlorpromazine was observed to be an effective antipsychotic agent, it was tested experimentally to uncover its mechanism of antipsychotic action. 

FIGURE 11 — 2. The dopamine receptor antagonist hypothesis of antipsychotic drug action for positive symptoms of psychosis in the mesolimbic dopamine pathway is shown here. Blockade of postsynaptic dopamine 2 receptors by a dopamine 2 antagonist acting in the mesolimbic dopamine pathway is hypothesized to mediate the antipsychotic efficacy of the antipsychotic drugs and their ability to diminish or block positive symptoms. 

It should now be obvious that the use of conventional antipsychotic drugs presents a powerful dilemma. That is, there is no doubt that conventional antipsychotic medications have dramatic therapeutic actions on positive symptoms of psychosis by blocking hyperactive dopamine neurons in the mesolimbic dopamine pathway. However, there are four dopamine pathways in the brain, and it appears that blocking dopamine receptors in only one of them is useful, whereas blocking dopamine receptors in the remaining three pathways may be harmful. 

Profound mood-stabilizing effects of the atypical antipsychotic drugs were observed once their antipsychotic effects were documented. These effects on mood appear to be quite independent of their effects on positive symptoms of psychosis. The most dramatic story may be how impressive the atypical antipsychotics are turning out to be for the treatment of bipolar disorder (Fig. 11 — 53). Although the best documented effect of these drugs is to reduce psychotic symptoms in the acute manic phase of bipolar disorder, it is clear that these agents also stabilize mood and can help in some of the most difficult cases, such as those marked by rapid cycling and mixed simultaneous manic-depressed states that are often nonresponsive to mood... 

As researchers learned more about the neurologic changes involved in psychosis, drugs were developed to specifically treat disorders rather than simply sedate the patient. These antipsychotic drugs, or neuroleptics, as some clinicians refer to them, represent a major breakthrough in the treatment of schizophrenia and other psychotic disorders. 

Consequently, antipsychotic drugs all share a basic mechanism of action that involves dopamine receptor blockade. It is apparent, however, that they are not all equal in their ability to affect specific sub-types of dopamine receptors, and that their effectiveness and side effects are related to their affinity and preference for certain receptors. As indicated earlier, other neurotransmitters may also be involved in the pathogenesis of psychosis, and differences in specific antipsychotic medications may be related to their ability to directly or indirectly affect these other transmitters as well as block dopamine influence. Future studies will continue to clarify how current antipsychotics exert their beneficial effects and how new agents can be developed to be more selective in their effects on dopamine and other neurotransmitter pathways. 

Antipsychotic drugs represent one of the major advances in the management of mental illness. Drugs are currendy available that diminish the symptoms of psychosis and improve a patient s ability to cooperate... 

Regardless of the cause of LSD psychosis, people with this condition usually respond to treatments for the mental illnesses their condition resembles. So, if their symptoms resemble psychosis, they generally respond to antipsychotic drugs. 

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