Family and Caregiver Schizophrenia Discussion Forum

Polypharmacy vs. Monotherapy

I generally like my son’s psychiatrist. What I don’t like is that he constantly prescribes more than one drug at a time. Currently, it’s olanzapine and quetiapine.

There is a good reason why polypharmacy is not a good idea: it can’t be evidence-based. That’s because researchers seldom if ever study 2-drug regimens and therefore there’s no evidence that it works.

There was a discussion on this board 4 years ago.Read Stan0542’s tragic story starting on Dec 17, 2017

Stan referenced this article: The Problem of Polypharmacy in Psychiatry


I wonder if there isn’t something in the guidelines we are studying about this?

The Depakote is for his seizures but his psychiatrist says it also has a “mood leveling” effect. The benztropine is for his drooling side effect. The clozapine is the main anti psychotic and has really worked wonders in the big picture.

Good suggestion. I searched for “poly” in the document and found this in a footnote: Association of Antipsychotic Polypharmacy vs Monotherapy With Psychiatric Rehospitalization Among Adults With Schizophrenia

This table shows that quetiapine monotherapy is very much worse than olanzapine monotherapy, which is very slightly worse than quetiapine and olanzapine together, which is what my son is on. Doesn’t say anything about levels of dosing though.

Also this:

The risk of psychiatric hospitalization, all-cause hospitalization, or death was not decreased significantly by adding any miscellaneous antipsychotic (most of those other than aripiprazole) to clozapine. However, including any other agent with quetiapine, which had the worst monotherapy response, resulted in a better outcome. At an aggregate level, the risk of psychiatric rehospitalization was 7% lower during any polypharmacy than any monotherapy period without censoring the first 90-day periods of antipsychotic treatment

That’s a good find caregiver1. I guess your son’s psychiatrist is within these guidelines prescribing the two together, assuming dosage is correct.

@Steadfast I’m actually surprised given Stan’s reference about how polypharmacy can’t be evidence-based. I wonder how much evidence there is in the review paper I referenced. How many people were observed to have a better outcome on quetiapine + olanzapine vs olanzapine monotherapy? At least it’s not zero, so I’m thankful for that.

What about quetiapine’s side effects? If the combo therapy is only slightly better, why not get rid of the quetiapine because of possible side effects ( possible heart rhythm (QT prolongation) being one of them)? Now I have to take him to get an ECG to see if this is happening. They are all constipating, and we’ve had to battle that too.

I sent an email referencing the article and table to my son’s psychiatrist asking him to consider olanzapine monotherapy because the benefit of adding quetiapine doesn’t seem to me to outweigh the risk. Will see what he says at the next meeting about a slow taper of the quetiapine.

Battling olanzapine side effects is a job in itself because of metabolic side effects.

Very good points caregiver1. I will be curious to see what sort of response you get.

Well I am on Latuda and Ziprasidone and I manage to work full time and lead a good life, etc. So, don’t rule it out totally just because there is less research on it.

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@Lirik The article says that polypharmacy for maintenance is preferable to monotherapy. Says that monotherapy may be better in the acute phase.

Our results revealed that, in general, antipsychotic polypharmacy was associated with an approximately 10% lower relative risk of psychiatric rehospitalization (corresponding to an approximately 6% lower absolute risk with an approximately 60% rehospitalization rate in the cohort) compared with antipsychotic monotherapy

Current treatment guidelines state that antipsychotic monotherapy should be preferred and polypharmacy should be avoided if possible. These recommendations reflect the recent evidence in high-quality studies on the acute-phase treatment. However, results from our study suggest that antipsychotic polypharmacy may be superior to monotherapy for maintenance treatment, which has not been examined with RCTs. Therefore, it should be acknowledged that statements about a preferential use of antipsychotic monotherapy for maintenance treatment of schizophrenia lack evidence, and that currently available evidence—although gathered with few nonrandomized cohort studies that have their own limitations—indicates the opposite. Therefore, the current treatment guidelines should modify their categorical recommendations discouraging all antipsychotic polypharmacy in the maintenance treatment of schizophrenia.

My only quibble is that adding drugs in the same class also means adding potential side effects, which I didn’t see mentioned in the article.

The authors state that the drugs should have “different receptor profiles”:

These results indicate that rational antipsychotic polypharmacy seems to be feasible by using 2 particular antipsychotics with different types of receptor profiles.

Latuda and Ziprasidone probably work on different systems in the brain.