An Update In Medications for Psychosis

Written by Dr. David Mulhall

A neuroleptic – specifically beneficial for treatment of psychosis was discovered in the late 1950’s – i.e. Chlorpromazine which was given the trade name Largactil as it had a “large action”.  The introduction of this medication and others following it was associated with a marked reduction in lengths of stay in hospital and a gradual reduction in the number of beds required for psychiatric care throughout the western world.  These medications were called the first generation or typical neuroleptics and continued until 1990 and the most powerful one in this group was Haloperidol.

At that it time is was recognized that  a significant number of patients still had a limited response to conventional treatments including medications and researchers looked at a medication Clozapine which had been used briefly early in the 1970’s but discontinued as had significant side effects.  It was however an extremely effective medication and when reintroduced with strict guidelines and blood count monitoring proved effective for treatment resistant schizophrenia.  It remains the “gold standard” in terms of effectiveness although limited to those who do not benefit from standard medications. 

Following the reintroduction of Clozapine a number of “second generation” neuroleptics were developed which had a significant impact on treatment prescribing practices.  These medications had minimal effects on movement disorders such as tremors or Parkinsonism and were better tolerated by patients.  However had significant metabolic side effects with marked increase in weight, elevated cholesterol and lipids as well as elevated glucose and vulnerability to diabetes.  Overall these medications show a modest benefit compared to the previous first generation antipsychotics such as Haloperidol. 

In recent years the trend amongst new medications coming to market has been a reduction in the metabolic side effects, i.e. weight gain, elevated cholesterol and glucose.  Two agents long available in the U.S. have become available in Canada in the past two years, one Zeldox/ Ziprasidone and two Abilify/Aripiprazole both with minimal effects on weight and glucose and lipid levels.  At present Ziprasidone is funded via Pharmacare but Abilify requires special authorization.

There is a series of additional medications being launched in the U.S. in the past two years including Latuda/Lurasidone again with the emphasis on reduced metabolic side effects. 

There does not appear to be an increase in potency in the newer medications in the past ten years and the largest trial comparing medications head to head, i.e. the CATIE trial confirmed that Clozapine remained the most potent medication followed by Olanzepine followed by Risperidone.

One factor limiting the development of new drugs is the significant cost involved in the process and overall there are significantly less new medications coming to market in all fields of medicine making it likely that we will be utilizing the current range of medications for some years. 

It is important to note that the use of medications is only one avenue of treatment along with significant impact in the development of psychosocial rehabilitation models to maintain individuals at their highest level of functioning and health with the reintroduction of hospitalized patients into the community.