Positive symptoms, of schizophrenia

Neuroleptics or antipsychotics suppress the positive symptoms of schizophrenia such as combativeness, hallucinations and formal thought disorder. Some also alleviate the negative symptoms such as affective blunting, withdrawal and seclusiveness. Neuroleptics also produce a state of apathy and emotional indifference. Most neuroleptics block dopamine D2-receptors but some, like clozapine, also block dopamine D4-receptors or serotonin 5-hydroxytryptamine2A-receptors. 

Initiation of behaviour Mesolimbic pathway to nucleus accumbens from VTA (AIO) Mesocortical pathways to prefrontal cortex from VTA (AIO) Animals Increases locomotor activity and intracranial self-stimulation Humans Hallucinations, psychoses (reward, reinforcement) Animals Decreases activity and self-stimulation Humans Reduces positive symptoms of schizophrenia D2 ... 

On this evidence one can confidently equate EPS with neuroleptic DA receptor (D2) antagonism in the striatum and possibly a reduction in the positive symptoms of schizophrenia through similar action in the limbic system (nucleus accumbens). 

It appears that an ideal neuroleptic may need to reduce DA activity in the mesolimbic system (nucleus accumbens) to counter the positive symptoms of schizophrenia, increase it in the prefrontal cortex to overcome negative symptoms and have little or possibly no effect on it in the striatum so EPSs do not arise (Fig. 17.9). No wonder we still await the ideal drug. 

Despite their importance in psychiatry, the neuroleptics are by no means cure-alls. Even patients that respond extremely well to neuroleptics remain disturbed. Specifically, though their florid hallucinations and delusions, the positive symptoms of schizophrenia, are alleviated, patients remain emotionally detached from the environment. This wallflower syndrome and related symptoms are commonly designated the negative symptoms of schizophrenia and often are the most disabling ones. The first glimmer of effective treatment of such negative symptoms came with the drug clozapine. 

Chlorpromazine (Thorazine). The first of the modem antipsychotics was developed in the early 1950s, not as an antipsychotic but as an antihistamine that could be used during surgery to minimize the amount of anesthesia needed. It was hoped that this would lessen the danger of shock (dangerously low blood pressure) during surgery. It was actually quite successful, but it was soon found to have other benefits. Of key importance, it could relieve the positive symptoms of schizophrenia. In the years to follow, this led to the production of other similar antipsychotics collectively known as the typical antipsychotics. 

In admittedly oversimplified terms, it is believed that hyperactivity of dopamine neurons in the mesolimbic pathway contribute to the positive symptoms of schizophrenia. All the typical antipsychotics are believed to work by reducing the activity of the mesolimbic dopamine pathway. More specifically, they do this by blocking dopamine receptors on the nerve cells. Over a period of 1-3 weeks, the dopamineblocking effect of the typical antipsychotic begins to relieve the positive symptoms of schizophrenia. 

The goals of treatment during the acute phase of illness are to reduce the positive symptoms of schizophrenia and to plan for extended treatment during the maintenance phase. Reducing the positive symptoms quickly is important for at least two reasons. First, the erratic behavior of an acutely psychotic patient can take a tremendous toll, risking arrest, loss of job, suicide, and the alienation of friends and family. Second, there is some evidence that psychosis itself is harmful to the brain. In other words, it may be that the longer the patient is actively psychotic, the worse the prognosis becomes. 

Underactivity of dopamine in mesocortical pathways, specifically those projecting to the frontal lobes, may account for the negative symptoms of schizophrenia (e.g., anergia, apathy, lack of spontaneity) (Davis et al. 1991 Goff and Evins 1998). In addition, this underactivity in the frontal lobes may serve to disinhibit mesolimbic dopamine activity via a corticolimbic feedback loop. Overactivity of mesolimbic dopamine is the result, which manifests as the positive symptoms of schizophrenia (e.g., hallucinations, delusions). 

Sellwood, W., Haddock, G., Tarrier, N., Yusupoff, L. Advances in the psychological management of positive symptoms of schizophrenia. Int. Rev. Psvchiatrv 6, 201-215, 1994. 

Use of Atypical Antipsychotics for Positive Symptoms of Schizophrenia and Related Disorders... 

Although the usefulness of the atypical antipsychotics is best documented for the positive symptoms of schizophrenia, numerous studies are documenting the utility of these agents for the treatment of positive symptoms associated with several other disorders (discussed in Chapter 10 see Fig. 10—2). Atypical antipsychotics have become first-line acute and maintenance treatments for positive symptoms of psychosis, not only in schizophrenia but also in the acute manic and mixed manic-depressed phases of bipolar disorder in depressive psychosis and schizoaffective disorder in psychosis associated with behavioral disturbances in cognitive disorders such as Alzheimer s disease, Parkinson s disease, and other organic psychoses and in psychotic disorders in children and adolescents (Fig. 11—52, first-line treatments). In fact, current treatment standards have evolved in many countries so that atypical antipsychotics have largely replaced conventional antipsychotics for the treatment of positive psychotic symptoms except in a few specific clinical situations. 

Figure 11.2. Schematic representation of ventral limbic circuits implicated in the positive symptoms of schizophrenia.

Q10 Haloperidol is an antipsychotic or neuroleptic agent. It is an antagonist at dopamine receptors, particularly of the D2 subtype. These drugs help to control the symptoms (mainly the positive symptoms) of schizophrenia by antagonizing the dopamine receptors in different brain areas, such as the frontal and temporal lobes. Antipsychotic agents, such as haloperidol, take days or weeks to achieve their therapeutic effect and may produce some motor disturbances. 

Haloperidol helps to control the positive symptoms of schizophrenia by antagonising dopamine receptors (D2 receptors) in several brain areas, but may produce motor disturbances. 

Fixed doses of amisulpride (100, 400, 800, and 1200 mg/ day) and haloperidol (16 mg/day) have been compared in a 4-week, double-blind, randomized trial in 319 patients with acute exacerbations of schizophrenia (33). Amisulpride 400 mg/day and 800 mg/day was effective in treating the positive symptoms of schizophrenia, with fewer extrapyramidal adverse effects than haloperidol,... 

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