Antipsychotics negative effects

Other Symptoms. Although they are not reflected in the DSM-IV criteria, it now appears that mood and cognitive symptoms also hinder the patient with schizophrenia. Depressed mood, often short of the duration or severity needed to diagnose major depression or schizoaffective disorder, is an all too common problem. Because the negative symptoms of the illness and certain antipsychotic side effects resemble depression, this was long overlooked. Indeed, depressed mood may in part explain the extremely high rates of attempted and successful suicides by those with schizophrenia. 

The second revolution began in the past 10 years with the arrival of the atypical antipsychotics. Although the atypicals are no panacea for schizophrenia, they represent an advance in at least three areas. First, they lessen the burden of antipsychotic side effects and therefore frequently increase adherence dramatically. Second, the atypicals may treat all of the schizophrenia symptom clusters (positive, negative, mood, cognitive), whereas the typical antipsychotics chiefly treat the positive symptoms. Third, atypical antipsychotics sometimes benefit patients whose schizophrenia is unresponsive to typical antipsychotics. 

Conventional antipsychotics improve symptoms of hyperactivity and impulsivity, but may have negative effects on learning and cognitive functioning as well as extrapyramidal side effects (e.g., dystonia and tardive dyskinesia) that limit their usefulness. The atypical antipsychotics risperidone, olanzapine, quetiapine, and ziprasidone have been used to control severe aggression in refractory cases of ADHD, particularly if conduct disorder or bipolar disorder coexists. More studies are needed to clarify their place in therapy. ... 

Risperidone (11) is a new type of an atypical antipsychotic with relatively pronounced effects on negative symptoms and low extrapyramidal side... 

The 5-HT3 receptor is found appropriately in mesocortical areas and while behavioural studies with their antagonists in rodents showed potential antipsychotic activity, they have proved ineffective in patients. 5-HTia agonists may be more useful. They have been found to increase the extracellular concentration of DA in the frontal cortex of rats but diminish apomorphine-induced stereotypy (striatal effect). So they could be of some benefit, especially against negative symptoms, without causing EPSPs (see Chapter 9). 

Compared to the older antipsychotics (first-generation antipsychotics), the more recently developed second-generation antipsychotics are associated with a lower risk of motor side effects (tremor, stiffness, restlessness, and dyskinesia) may offer greater benefits for affective, negative, and cognitive symptoms and may prolong the time to psychotic relapse. 

Roche for their inhibitor RG1678. This trial provides compelling evidence that GlyT-1 inhibitors show promise as a novel class of antipsychotics that are effective at ameliorating the negative symptoms and cognitive dysfunction associated with schizophrenia. 

Quetiapine (Seroquel). Quetiapine is the fourth of the atypical antipsychotics introduced in the United States. It is effective in both positive and negative symptoms of schizophrenia within a dose range of 150 to 750mg/day in two divided... 

Parkinsonism. As will be discussed later, dopamine-blocking antipsychotics and rarely other psychotropic medications can produce symptoms that resemble Parkinson s disease. This includes an expressionless face, slowed movement, and a stooped posture. In many respects, medication-induced parkinsonism resembles both depression and the negative symptoms of schizophrenia. Again, one must decide if it is the illness or the medication. Do you decrease the medication to remedy the side effect Or do you increase the medication to treat the illness, anticipating that a higher dose may prove more beneficial (though this is not always what is found) ... 

The conventional antipsychotics have little effect on the negative psychotic symptoms such as autism, stupor and emotional withdrawal. The so-called atypical antipsychotics, or second-generation antipsychotics, like the heterocyclic compound risperidone, the benzamide sulpiride and several diben-zepines of which clozapine is the best known, have a broader spectrum which means that they also have an effect on the negative psychotic symptoms. Most share a common attribute of working on serotonin receptors as well as dopamine receptors. They have a low risk of extrapyramidal side effects. 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

In addition to the somatic side-effects of neuroleptics, there are a number of important psychiatric side-effects, such as demotivation or indifference (a direct effect of most drugs, actually part of the definition of the neuroleptic effect). This may mimic the negative features of the illness and may lead to prescriptions of an antidepressant when a reduction in dose or change of antipsychotic may be more appropriate. A second key problem is anxious activation or akathisia. This dose-dependent dysphoric state may lead to an apparent worsening in the clinical picture and accordingly an increase in antipsychotic dose rather than decrease and may be so intolerable as to lead on to suicide. 

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