Side effects antipsychotics

With respect to other ethnic groups, African Americans may have a differential sensitivity to weight gain on clozapine (de Leon etal, 2007). They may also require lower doses than Caucasians (Kelly et al, 2006) and inter-individual as well as ethnic responsiveness maybe partly explained by differences in dopamine receptor polymorphisms (Hwang et al, 2005). It is conceivable that side effects may also be differentially expressed based on pharmacodynamic differences resulting from polymorphisms in other receptor types (histaminergic, muscarinic, etc.). This area remains largely unexplored with respect to ethnic differences in antipsychotic side effects. 

Table 71-3 presents the relative incidence of common categories of antipsychotic side 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. 

We prefer low doses of atypical antipsychotics as a first-line treatment. In this way, the threat of extrapyramidal symptoms is largely avoided without having to use a second anticholinergic medication to offset antipsychotic side effects. Risperidone 0.25-0.5mg/day, olanzapine 2.5mg/day, quetiapine 25mg/day, ziprasidone 20mg/day, or aripiprazole 2.5-5mg/day are reasonable starting doses. The typically higher doses used to treat schizophrenia are usually not necessary. 

Typical Versus Atypical Antipsychotics. We discussed at length in Chapter 5 just what makes a typical antipsychotic typical and what makes an atypical antipsychotic atypical. We ll spare you a rehash of that lengthy discussion however, it is important to note that all typical antipsychotics are not created equal. Although they all work by blocking the dopamine D2 receptor, their potency at this receptor varies up to 100-fold. In addition, antipsychotic side effects are not due solely to dopamine receptor blockade. In many cases, the most troublesome side effects result from blocking other receptor types including histamine, acetylcholine, and the norepinephrine alpha-1 receptor system. 

Using antipsychotics Side effect profiles, special concerns in the elderly. (1989, April). Psychiatric Times Supplement, pp. l t. 

The scope of the present chapter is to provide an overview of the current state of pharmacogenetics in schizophrenia treatment. The most promising pharmacogenetic findings will be presented for both antipsychotic response and the most commonly studied antipsychotic side effects. The application of pharmacogenetics to schizophrenia treatment will also be discussed, with an emphasis on the clinical utility of pharmacogenetic testing and directions for future research. 

Patients with AD are more sensitive to antipsychotic side effects than other patient groups. Increased sensitivity to antipsychotic side effects in the elderly appears to be the result of altered pharmacodynamics rather than altered pharmacokinetics. Particularly problematic side effects are extrapyramidal side effects, postural hypotension caused by a-adrenergic blockade, and anticholinergic effects, including increased confusion, urinary retention, constipation, and dry mouth. For a more detailed description of antipsychotic side effects see Chap. 66 on schizophrenia. Overall, fewer side effects are seen with tlie newer atypical antipsychotics, making them a preferred choice for treatment of psychosis or aggression in the AD patient. Effective doses of antipsychotic medications are much lower than those typically used to treat schizophrenia (see Table 63-8). The rule of thumb is to start low and go slow. ... 

I Sedation and Cognition. Sedation must be recognized as an antipsychotic side effect and not as an indication of therapeutic effect. It occurs more frequently with antipsychotics with antihistaminic properties. Chlorpromazine, thioridazine, mesoridazine, clozapine, olanzapine, and quetiapine are most frequently implicated. Administration of most or all of the daily dosage at bedtime (depending on the drug half-life) can decrease daytime sedation and in some patients eliminate the need for hypnotic agents. Sedation occurs early in treatment... 

Extra-pyramidal side effects - abnormalities of movement due antipsychotic side effect First pass metabolism - metabolism on first passage through the liver Fungicidal - kills fungi Fungistatic - inhibits fungal growth... 

It has been suggested that high affinity for certain 5-HT receptors is a possible method for reducing extrapyramidal side effects observed with antipsychotics. LiabiUty for extrapyramidal side effects has been hypothesi2ed to be related to the ratio of the affinity between dopamine receptor... 

Antipsychotics are not indicated for the treatment of withdrawal, except when hallucinations or severe agitation are present (Naranjo and Sellers 1986), in which case they should be added to a benzodiazepine. In addition to their potential to produce extrapyramidal side effects, antipsychotics lower the threshold for seizures, which is particularly problematic during alcohol withdrawal. 

Chlorpromazine had been shown to produce a tranquil state in animals and since it had a similar effect in humans it became known as a major tranquiliser but the term is rarely used today. Sometimes the drugs used to treat schizophrenia are called anti-psychotics but more commonly neuroleptics. Leptic means to activate (take hold of) and in animals these compounds produce a state of maintained motor tone known as catalepsy. This is an extrapyramidal effect and in schizophrenics the neuroleptics can cause a number of extrapyramidal side-effects (EPSs) including Parkinsonism. The new term neuroleptic is unsatisfactory as a description of clinically useful drugs. It really describes a condition (catalepsy) seen in animals and is more indicative of a compound s ability to produce EPSs than to treat schizophrenia. Antipsychotic is more descriptive but could imply a more general efficacy in psychoses than is the case. It would seem more appropriate to call a drug that is used to treat schizophrenia an antischizophrenic just as we use the terms antidepressant or antiepileptic irrespective of how the drug works. Despite such personal reservations, the term neuroleptic will be used in this text. 

Compare the side-effect profiles of individual antipsychotics. 

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. 

Second-generation antipsychotics as a class are heterogeneous with regard to side-effect profiles. Many second-generation antipsychotics carry an increased risk for weight gain and for... 

TABLE 34-4. Comparative Side Effects among the Second-Generation Antipsychotics and Haloperidol... 

TABLE 34-7. Side Effects of First-Generation (Typical) Antipsychotics... 

Antipsychotics can be safe and effective for the treatment of psychosis in the elderly, if used at lower doses than those commonly used in younger adults. Older adults are particularly vulnerable to the side effects of FGAs. Parkinsonian symptoms... 

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