Antipsychotics psychiatric effects

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

The short-acting clomethia2ole [533-45-9] (1), sometimes used as therapy for sleep disorders ia older patients, shares with barbiturates a risk of overdose and dependence. Antihistamines, such as hydroxy2iae [68-88-2] (2), are also sometimes used as mild sedatives (see HiSTAMlNES AND HISTAMINE antagonists). Antidepressants and antipsychotics which have sedative effects are used to treat insomnia when the sleep disorder is a symptom of some underlyiag psychiatric disorder. 

Schizophrenia is perhaps the most debiUtating psychiatric illness in modem medicine, affecting about 1% of the general population. Many of those affected require institutionalization (180). Unfortunately, the compounds available to treat this disorder are not hiUy effective in treating the spectmm of symptoms in all patients. Adverse effects are also a problem (181). In addition, available antipsychotic (neuroleptic) dmgs (Table 5) can at most only provide symptomatic rehef. 

In noncancer-related pharmacology, GSK3 is inhibited by lithium at therapeutic concentrations, implying that the long-established effectiveness of lithium in the treatment of psychiatric mood disorders (and more recently as a neuroprotective agent) may be linked to GSK3 inhibition. Antipsychotics such as haloperidol... 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

A role for the 5-HT7 receptor in the regulation of circadian rhythms has been implicated. As discussed above, 5-HT has been known for some time to induce phase shifts in behavioral circadian rhythms and modulate neuronal activity in the suprachiasmatic nucleus, the likely site of the mammalian circadian clock. The pharmacological characteristics of the effect of 5-HT on circadian rhythms are consistent with 5-HT7 receptor. Moreover, mRNA for the 5-HT7 receptor is found in the suprachiasmatic nucleus. There is also increasing evidence that the 5-HT7 receptor may play a role in psychiatric disorders. The regional distribution of 5-HT7 receptors in brain includes limbic areas and cortex. Atypical antipsychotics, such as clozapine and risperidone, and some antidepressants display high affinity for this receptor. In the periphery, 5-HT7 receptors havebeenshown to mediate relaxation of vascular smooth muscle. 

Selection of an antipsychotic should be based on (1) the need to avoid certain side effects, (2) concurrent medical or psychiatric disorders, and (3) patient or family history of response. Fig. 71-1 is an algorithm for management of first episode psychosis. 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

Probably the greatest advances in psychiatric medications of the last 15 years have involved the neurotransmitter serotonin. First was the arrival of serotonin-specific antidepressants with fewer side effects and greater safety than their predecessors. More recently, atypical antipsychotics have highlighted the importance of serotonin-dopamine interactions in the optimal treatment of schizophrenia and other psychotic disorders. While these are indeed significant advances, medications that alter serotonin activity are not without their own side effect burden. 

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. 

Muller and Schoneich (1992) also reported on favorable experience with intensive outpatient psychotherapy combined with antipsychotic drug treatment. On the basis of a before-and-after comparison over 2x5 years in a university outpatient clinic, they were able to show that the duration of rehospitalizations required by 89 patients could be reduced from a mean of 10 weeks to 2 weeks per year when a special schizophrenia outpatient service offering individualized psychotherapy and psychosocial treatment was available to the patients instead of the routine psychiatric outpatient service. A beneficial effect of psychotherapy was demonstrated both in those patients taking antipsvchotics continuously for long-term prophylaxis and in those taking the drugs intermittently when prodromal symptoms appeared in order to prevent relapse. 

Assessment of physical, as well as psychiatric status, is also critically important. The presence of intercurrent medical disorders, as well as any medication used to manage them, increases the likelihood of an adverse outcome with an otherwise appropriate medication. With a recent history of myocardial infarction, certain tricyclic antidepressants (TCAs) or low-potency antipsychotics might be contraindicated due to potential adverse effects on cardiac function. Another example is the avoidance of carbamazepine in a bipolar patient with a persistently low white blood cell count. Finally, b-blockers are typically contraindicated in a patient with asthma. 

FIG. 5-3. Effects of neuroleptics on thought disorder and behavioral symptoms of schizophrenia. BPRS, Brief Psychiatric Rating Scale TDI, Thought Disorder Index. (From Davis JM, Barter JT, Kane JM. Antipsychotic drugs. In Kaplan HI, Sadock BJ, eds. Comprehensive textbook of psychiatry, 5th ed. Baltimore Williams Wilkins, 1989 1604, with permission.)... 

Clonazepam. Clonazepam is marketed primarily for petit mal variant, myoclonic, and akinetic seizures. It also has had wide psychiatric application, including the treatment of acute mania or other agitated psychotic conditions, usually in combination with lithium or antipsychotics. The literature on clonazepam s efficacy for acute mania is based on the work of Chouinard (120) and coworkers who compared this agent with placebo or standard treatments for acute mania. As noted earlier, however, another group from Montreal found that comparable doses of lorazepam were more effective than clonazepam for acute mania (119). 

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