Antipsychotic treatment

Trigclic Antidepressants. Imipramine (38) was introduced in the late 1950s as one of the first pharmacotherapies for depression. At that time, chlorproma2ine [50-53-3] was the first effective antipsychotic treatment to be discovered. Researchers looked for similar chemical stmctures and imipramine was found to be effective in the symptomatic treatment of depression. Over the years, other congeners, such as desipramine (39), amitriptyline (40), and dothiepin (41), were synthesized and shown to be clinically efficacious antidepressant dmgs (121). These substances, known under the general mbric of tricycHc antidepressants, share a basic chemical stmcture comprising... 

Educate patients and families about schizophrenia, treatments, and the importance of adherence to antipsychotic treatment. 

Kaiser, R., Konneker, M., Henneken, M. et al. (2000). Dopamine D4 receptor 48-bp repeat polymorphism no association with response to antipsychotic treatment, but association with catatonic schizophrenia. Mol. Psychiatry, 5, 418-24. 

Masellis,M.,Basile,V. S.,Ozdemir, V. etal. (2000). Pharmacogenetics of antipsychotic treatment lessons learned from clozapine. Biol. Psychiatry, 47, 252-66. 

Emsley RA. Partial response to antipsychotic treatment the patient with enduring symptoms. J Clin Psychiatry 1999 60(Suppl 23] 10-13. 

Muller, D. J., and Kennedy, J. L. (2006) Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics. 7, 863-887. 

In cases where there is a strong family history of schizophrenia and the symptoms are particularly ominous, many clinicians will recommend antipsychotic treatment during the prodromal phase. Low doses of an atypical antipsychotic (other than clozapine) probably offer the best promise of a treatment response with a minimal risk of problematic side effects. 

The second question has the greater impact on treatment choice. There are four major possibilities to consider when trying to determine why the patient has relapsed. First, it may have been treatment failure due to inadequate dosing of the antipsychotic. Second, a psychosocial stressor may have triggered the exacerbation despite otherwise adequate antipsychotic treatment. Third, the patient may not be adherent with the antipsychotic. Finally, this may represent the natural course of this patient s illness. 

Kablinger AS, Freeman AM. Prodromal schizophrenia and atypical antipsychotic treatment. J Nerv Ment Dis 2000 188(10) 642-652. 

Madhusoodanan S. Introduction antipsychotic treatment of behavioral and psychological symptoms of dementia in geropsychiatric patients. Am J Geriatr Psychiatry 2001 9(3) 283-288. 

Delusional Disorder and Schizotypal Personality Disorder. In onr experience, patients with BPD at times resemble those with Clnster A personality disorders or those with an Axis 1 psychotic disorder. Psychotic symptoms in the BPD patient, although intense, tend to arise in the context of some stressor and to be relatively short-lived. This usually takes the form of a brief psychotic disorder. Placing the BPD patient in a structured and supportive environment usually hastens the resolution of these psychotic symptoms. By contrast, the psychotic symptoms of a patient with a delusional disorder or a Cluster A personality disorder are long-term and potentially intractable even with antipsychotic treatment. 

There are, of course, risks with long-term use of conventional antipsychotics. The most concerning is an irreversible movement disorder known as tardive dyskinesia. Nevertheless, some particularly fragile patients with BPD may require long-term antipsychotic treatment. If so, atypical antipsychotics are recommended. 

Tardive Dyskinesia (TD). As mentioned previously, TD is a potential side effect of long-term treatment with typical antipsychotics it is believed to be very rare but possible after atypical antipsychotic treatment. Although we now know that TD is not irreversible in all patients, about half will recover after discontinuation of the antipsychotic and the passage of several months time, others will exhibit the symp-... 

Buspirone has no established antipsychotic activity do not employ in lieu of appropriate antipsychotic treatment. 

Switching from other antipsychotics - Nh e immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, gradual discontinuation may be more appropriate for others. In all cases, minimize the period of overlapping antipsychotic administration. 

The antischizophrenic actions of these drugs may not consist simply of postsynaptic blockade of hyperactive dopamine systems. Such a blockade occurs within hours, while most symptoms improve over weeks. This discrepancy in the latency to therapeutic effect has been hypothesized to be linked to drug-induced changes in dopaminergic activity after initiation of therapy, dopamine turnover increases, but after continued antipsychotic treatment, tolerance develops and dopamine metabolism returns to normal. This downward adjustment of dopaminergic activity is consistent with the decreased plasma concentrations of the dopamine metabolite homovanillic acid, an observation that correlates temporally with the clinical response to drug treatment. 

Katz IR. Optimizing atypical antipsychotic treatment strategies in the elderly. 1 Am Geriatr Soc 2004 52 S272-S277. 

The difficulties that are generally most problematic during the initial phase of antipsychotic treatment of young people are the EPS and sedation. These adverse events often lead to significant management difficulties for the clinician, but also likely lead to reduced acceptability and compliance with treatment. Concerns... 

It is recommended that neurological side effects be monitored carefully throughout the course of antipsychotic treatment. Rating scales can assist in monitoring for EPS and the involuntary movements seen in tardive dyskinesia. These include the Neurological Rating Scale (Simpson and Angus, 1970), the Barnes Akathisia Scale (Barnes, 1989), and the Abnormal Involuntary Movement Scale ([AIMS] National Institute of Mental Health, 1985). 

FIGURE 41.1 A decision tree for antipsychotic treatment selection in childhood and adolescence (adapted and modified from Clark and Lewis 1998). 

It is recommended that first-episode patients remain on antipsychotic treatment for a period of 1 to 2 years as a measure to prevent relapses. 

These authors also examined which medications were prescribed to patients with specific diagnoses. The majority of antidepressants were prescribed for patients with major depression, dysthymia, or bipolar disorder. Antipsychotics were prescribed frequently for conduct/oppositional disorder, psychosis, and major depression or dysthymia. In the state hospital, the proportion of nonpsychotic patients who received antipsychotic treatment depended on patients age thus, the frequency of children who were not diagnosed with a psychotic disorder but who were treated with antipsychotic medication was greater among children 12 years and younger, in contrast to children ages 13 to 18 years. 

Some patients will decline ECT, and the available data suggest that combination antidepressant/antipsychotic treatment or amoxapine may be equally effective. Given the preponderance of data supporting TCA/antipsychotic combinations in the treatment of PMD, it may be reasonable to consider TCA combinations before other antidepressant combinations. Currently, the literature shows debates as to whether the SSRIs are as efficacious as the... 

A schizophreniform psychosis can follow administration of single or multiple, usually high, doses of SNA. Allen and Young reported on nine patients seen over a 13-mo period at an Army hospital with SNA psychosis within a week of multiple exposures.2 Despite antipsychotic treatment, three had not recovered from the residua of their psychosis 30, 60, and 90 d later. 

P. N. Jayakumar, B. N. Gangadhar, G. Venkatasubramanian, S. Desai, L. Velayudhan, D. Subbakrishna and M. S. Keshavan, Fligh energy phosphate abnormalities normalize after antipsychotic treatment in schizophrenia a longitudinal P MRS study of basal ganglia. Psychiatry Res., 2010,181, 237-240. 

In view of the large number of potential adverse effects, the benefits and risks of antipsychotic treatment have to be weighed carefully against each other in each individual patient the unrestricted prescription of these medications is just as unwarranted as total abstinence from medications. 

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