Antipsychotic drugs history

Shen, W.W. (1999a) A history of antipsychotic drug development. Compr Psychiatry 40 407-414. 

The 2004 Practice Guideline for the Treatment of Patients With Schizophrenia recommends indefinite maintenance treatment for patients who have had at least two episodes of psychosis within 5 years or who have had multiple previous episodes (Lehman et al. 2004). Maintenance therapy should involve the lowest possible doses of antipsychotic drugs, and patients should be monitored closely for symptoms of relapse. If the patient is compliant with treatment, oral medications are usually sufficient. However, if the patient s treatment history suggests that the patient may not reliably take daily oral medication, a long-acting depot preparation may be indicated. 

Evidence of violence, sexual abuse, or attempted suicide. History of psychiatric interventions, including antipsychotic drugs or ECT. 

Recently, a large study in the USA (CATIE) reported that perphenazine was as effective as atypical antipsychotic drugs, with the modest exception of olanzapine, and concluded that typical antipsychotic drugs are the treatment of choice for schizophrenia based on their lower cost. However, this study did not adequately consider the risk of tardivedyskinesia or the treatment history of patients in the design of this study. 

Serotonin-dopamine hypothesis. On the basis of the studies of both 5HT and DA in OCD, it seems possible that at least in some forms of OCD (e.g., OCD with a history of Tourette syndrome), both 5HT and DA transmitter systems may be involved in the pathophysiology of symptoms. It is not clear whether the primary abnormality is in 5HT function, DA function, or serotonin-dopaminergic balance. This hypothesis is supported by many preclinical data, which suggest that important anatomic and functional interactions exist between serotonergic and dopaminergic neurons. This will be discussed in detail in Chapter 11 in the sections on antipsychotic drugs that work simultaneously on DA and 5HT receptors. 

History of the disease model of antipsychotic drug action... 

The widespread use of neuroleptics has unleashed an epidemic of neurological disease on the world. Even if TD were the only irreversible disability produced by these drugs, this would be among the worst medically induced disasters in history. In reality, the antipsychotic drugs also reduce the quality of life, cause multiple severe and potentially lethal physical disorders, and shorten the life span. 

Akathisia has been reported in 16% of patients taking olanzapine (SEDA-21, 56). Three patients developed severe akathisia during treatment with olanzapine (20-25 mg/day) (87). In two, the akathisia resolved after withdrawal of olanzapine and in one of those olanzapine was well tolerated when reintroduced in combination with lorazepam. In the third patient, the akathisia was controlled by dosage reduction. A 33-year-old man with AIDS and a prior history of extrapyramidal symptoms with both typical antipsychotic drugs and risperidone developed dose-dependent akathisia with olanzapine 15-19 mg/day the akathisia responded to dosage reduction and beta-blockade (88). 

Obsessive-compulsive symptoms developed in a 26-year-old Chinese woman taking risperidone for a chronic schizophrenic illness (134). She had no history of obsessive-compulsive symptoms. Risperidone 2 mg/ day, benzhexol 2 mg/day, and diazepam 10 mg at night had been prescribed after she had had adverse effects with other antipsychotic drugs. 

A 47-year-old man with alcohol abuse took disulfiram (236). He developed a psychosis while taking it and for 2 weeks after. He stated that he had not taken alcohol. He was successfully treated with antipsychotic drugs. Afterwards it was discovered that his family history was positive for schizophrenia it is therefore possible that he was more vulnerable to develop psychosis due to disulfiram. 

HRT, like the last two issues I am going to cover here, came to a critical point in the first three or four years of the new millennium. However, history is not yet complete on any of these issues, indeed one often wonders whether it ever can be - e.g. with the return of previously withdrawn drugs like thalidomide and clozapine. The latter is an antipsychotic drug which was first introduced in the 1970s and then withdrawn following reports of agranulocytosis, i.e. absence of white blood cells. It was reintroduced with compulsory blood monitoring around 1990. 

Nervous system In a case-control analysis nested within a cohort of 26157 community-dwelling patients (mean age 76 years) with at least one antipsychotic drug prescription in the Netherlands, there were 518 hospital admissions for cerebrovascular adverse events [23 ]. For each case, four randomly selected controls, matched by sex and age, were sampled from the cohort. Current and recent exposure to antipsychotic drugs was associated with an increased risk of cerebrovascular adverse events compared with non-users (OR=1.7 95% CI=1.4, 2.2). The OR for a history of use less than a week was 9.9 (5.7,17). The risk fell with time and was comparable to the risk in on-users after 3 months (OR 1.0 95% Cl=0.7,1.3). 

High-potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to or in combination with antipsychotics for acute mania, agitation, anxiety, panic, and insomnia or in those who cannot take mood stabilizers. Lorazepam IM may be used for acute agitation. A relative contraindication for long-term benzodiazepines is a history of drug or alcohol abuse or dependency. 

This group investigated patients presenting with acute schizophrenic symptoms who underwent a drug-free washout period, received lithium only initially, and then antipsychotics later (374). Lithium was ineffective for classic schizophrenia, but some patients who met criteria for schizophreniform disorder did respond to lithium. Whether schizophreniform illness is a variant of mood disorders (a reasonable hypothesis in view of their lithium response) or a separate entity that is lithium-sensitive is still unclear. It is known that these patients have family histories that include mood-disordered as well as schizophrenic relatives. In a small pilot study, physostigmine (a drug with possible antimanic but no antipsychotic properties) benefited schizophreniform patients who responded to lithium, but had no effect in those who did not (Carver DL, personal communication). 

---