Side effects atypical

Normally, dietary tyramine is broken down in the gastrointestinal tract by MAO and is not absorbed. In the presence of MAOI, however, all of its potent sympathomimetic actions are seen. Other side effects of MAOI include excessive CNS stimulation, orthostatic hypotension, weight gain, and in rare cases hepatotoxicity. Because the monoamine oxidase inhibitors exhibit greater toxicity, yet no greater therapeutic response than other, newer agents, clinical use has been markedly curtailed. The primary use for MAOIs is in the treatment of atypical depressions, eg, those associated with increased appetite, phobic anxiety, hypersomnolence, and fatigues, but not melancholia (2). 

Figure 17.9 Schematic representation of the proposed activity profile of an ideal neuroleptic. The figure shows DA pathways to the prefrontal cortex, mesolimbic nucleus accumbens and striatum the effects required for an ideal drug on the DA influence and symptoms there and to what extent they are met by most typical and atypical neuroleptics and by clozapine. Note that while all atypical neuroleptics induce few extrapyramidal w side-effects (EPSs) few of them, apart from clozapine, have much beneficial effect in overcoming negative symptoms of schizophrenia ...

The adverse side-effects of the TCAs, coupled with their toxicity in overdose, provoked a search for compounds which retained their monoamine uptake blocking activity but which lacked the side-effects arising from interactions with Hj, aj-adreno-ceptors and muscarinic receptors. One of the first compounds to emerge from this effort was iprindole, which has an indole nucleus (Fig. 20.3). This turned out to be an interesting compound because it has no apparent effects on monoamine uptake and is not a MAO inhibitor. This, together with its relatively minor antimuscarinic effects, led to it commonly being described as an atypical antidepressant. Mechanisms that could underlie its therapeutic actions have still not been identified but, in any case, this drug has now been withdrawn in the UK. 

What are the expected differences in side-effect profiles between ethnic groups, in particular with selective serotonic re-uptake inhibitors and atypical antipsychotics Can the morbidity of medication side effects be reduced, hence increasing treatment compliance and effectiveness ... 

Agranulocytosis A severe form of neutropenia where the number of neutrophils (the major type of leucocyte or white blood cell) is very low, so reducing an individual s ability to fight infection. It is a potentially serious side effect of the atypical antipsychotic clozapine. 

Non-motor signs of the disorder are also treatable with symptomatic medications. The frequent mood disorder can be treated with standard antidepressants, including tricyclics (such as amitryptiline) or serotonin reuptake inhibitors (SSRIs, such as fluoxetine or sertraline). This treatment is not without risks in these patients, as it may trigger manic episodes or may even precipitate suicide. Anxiety responds to benzodiazepines, as well as to effective treatment of depression. Long-acting benzodiazepines are favored over short-acting ones because of the lesser abuse potential. Some of the behavioral abnormalities may respond to treatment with the neuroleptics as well. The use of atypical neuroleptics, such as clozapine is preferred over the typical neuroleptics as they may help to control dyskinesias with relatively few extrapyramidal side-effects (Ch. 54). 

Nevertheless, some atypical antipsychotic drugs, such as clozapine and olanzapine, have been linked to substantial weight gain, hyperlipidemia and type II diabetes, a new range of medically serious side-effects. 

The same can be said for treating clients who have schizophrenia and other psychotic disorders. They must be stabilized in order to make progress in therapy. As mentioned in Chapter 2, antipsychotic drugs now allow marked improvement among clients with schizophrenia, and the newer, atypical antipsychotic drugs have fewer side effects so clients are more likely to comply with taking their... 

There are numerous antidepressant medications on the market (table 7.1). Following development of monoamine oxidase (MAO) inhibitors were tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), and several atypical antidepressants (Baldessarini 1996). Successive generations of antidepressants have not necessarily become more effective in treating depression, but rather offer more favorable side-effect profiles—a crucial factor in effective clinical pharmacotherapy. An effective medication is not useful if its side effects are intolerable. 

Future directions for research on hypericum may continue the work done in clinical efficacy. More specifically, studies may be of interest that examine its effects in treatment of more severe depression and different subtypes of depression. The comparative efficacy of different hypericum preparations could be further investigated, and optimum dosages need to be established (Linde et al. 1996). Further work is needed to compare hypericum s efficacy and side effects with those of the SSRIs or atypical antidepressants, because published studies to date have only compared it with tricyclics. 

The traditional scheme is complicated by the fact that some antidepressants exhibit characteristics of more than one class. For example, clomipramine, a tricyclic antidepressant (TCA) with side effects and toxicity similar to other TCAs, works more like the selective serotonin reuptake inhibitors (SSRls). Similarly, venlafaxine and duloxetine, which are usually grouped with the atypical antidepressants, have a side effect and safety profile comparable to the SSRls. Although a classihcation system based on mechanism of action offers some advantage (see Table 3.7), even this scheme is limited by the fact that antidepressants that work in the same way may have widely divergent side effect and safety profiles. In the following discussion, the traditional classification system is adopted. Although fraught with problems and inconsistencies. 

When starting a SSRI, the abrupt increase in serotonin may cause side effects. In the brain, the short-term effects include headache, sleep disturbance, nervousness, anxiety, and tremulousness. The digestive system effects include nausea, loose stools, decreased appetite, and indigestion. Most of these effects are mild and shortlived or can be managed with over-the-counter remedies. Nausea, for example, can be minimized by taking a SSRI after meals. These effects are also commonly seen with venlafaxine and duloxetine, atypical antidepressants that block serotonin reuptake like the SSRIs. 

Trazodone (Desyrel). Trazodone was the first of the atypical antidepressants and was actually introduced prior to the SSRIs. It does not have the serious cardiac toxicity or anticholinergic side effects of the TCAs and was the most popular antidepressant until the arrival of the SSRIs. It is approved for the treatment of depression and is also commonly used in low doses to treat agitation in demented patients and insomnia. 

Risperidone (Risperdal). Risperidone is also approved by the FDA for the treatment of acute mania. It acts as an atypical antipsychotic at doses up to 4-6mg/day. Over this dose, and at lower doses in children and the elderly, risperidone acts more like a typical antipsychotic in that extrapyramidal side effects are common. 

Quetiapine (Seroquel). Another atypical antipsychotic, quetiapine has also been approved by the FDA for the treatment of acute mania. It is usually administered twice daily at doses of 150-750mg/day. Like its counterparts, quetiapine is a well-tolerated medication. Its common side effects are drowsiness, dizziness, and headache. It causes less weight gain than olanzapine or clozapine but more than ziprasidone or aripiprazole. Quetiapine also does not cause agranulocytosis nor does it increase the risk of seizures. It can occasionally cause mild changes in liver function tests, but these usually return to normal even if the patient continues taking quetiapine. 

Carbamazepine is also most beneficial for patients with mixed episodes and rapid cycling. However, many patients find the side effects of carbamazepine more troublesome than those of valproate, and becanse carbamazepine has a penchant for nntoward drug-drug interactions, we reserve the use of carbamazepine for those patients who are unable to tolerate valproate, lithium, and the atypical antipsychotic... 

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