June 1, 2012

First-Episode Schizophrenia Treatment Dilemma: Should We Switch or Keep Going?

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Juan A. Gallego, MD

The Zucker Hillside Hospital, Glen Oaks, and The Feinstein Institute for Medical Research, Manhasset, NY


As a psychiatrist treating patients with first-episode
schizophrenia who are enrolled in a randomized controlled trial, I often
encounter the following question from my psychiatrist colleagues who are
co-treating our patients in the inpatient units: “Can we switch
medication? The patient is still psychotic!” Repeatedly, I tell them that
the acute treatment trial is 16 weeks long and that some first-episode patients
take up to 16 weeks to respond to a single antipsychotic. Often, they look at
me with confused and incredulous faces, but, despite their doubts, they agree
to continue the same antipsychotic. I must admit that, at the beginning, I was
equally incredulous; however, seeing patients improve again and again after a
very gentle titration schedule over 16 weeks of treatment made me aware that
this approach really works. In fact, in many cases, my job consists of
decreasing unnecessarily high doses prescribed by inpatient unit psychiatrists
and telling the patient and family about the lengthy but judicious treatment
that will take place throughout 16 weeks, without forgetting to instill in them
hope and trust in this treatment approach.

Recent studies—most of them examining multiepisode patients
but also 2 studies with first-episode patients—have found that lack of response
after 2 weeks of antipsychotic treatment is associated with subsequent lack of
response, usually assessed after 6 to 12 weeks of treatment. However, my
experience has been different. Briefly, colleagues and I found that an
important number of first-episode patients take up to 16 weeks to fulfill
response criteria and that early lack of response was not a meaningful
predictor of subsequent nonresponse.1 In trying to understand the
difference in findings, a few things came to mind. First, our acute treatment
trial lasted 16 weeks, a period significantly longer than all other studies.
Second, we included only patients who did not respond after 2 weeks of
treatment to mirror the dilemma faced by clinicians in real life, ie, whether
or not to switch medication after patients have not improved. Third, we used
absolute improvement of positive symptoms (a rating of mild or better) as our
endpoint criterion for treatment response, as opposed to other studies that
used a percentage of improvement in symptoms from baseline as their criterion
for response.

Whether these methodological differences are responsible for
the difference in results is still unknown. However, I would like to hear
opinions from others. What approach are you implementing in clinical practice?
Have you had positive results? Are patients receptive or resistant to your

Now, what should researchers do? Is the evidence strong
enough to advocate for a delayed switch to be included in treatment guidelines?
Should we keep trying to understand this phenomenon and design new studies with
an early-switch component, like the one by Kinon et al2? Should we
perhaps focus more on molecular biomarkers as opposed to clinical ratings?

While some of these questions get clarified, I will continue
to treat my first-episode patients by using a gentle dosing approach over 16

Financial disclosure:Dr Gallego
had no relevant personal financial relationships to report.

Category: Schizophrenia
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20 thoughts on “First-Episode Schizophrenia Treatment Dilemma: Should We Switch or Keep Going?

  1. as psychiatry/medicine become more and more a”business of quick med-checks/Rx”, 16 week gentle titration, eventhough sounds good, is a luxury you and the patient cannot afford.
  2. In Pakistan patients pay for their illness and if you do not find at least fifty percent improvement in four weeks you are hard pressed by patients and their families to switch. This is what I found in my practice here
  3. I will definetly vote in favor of keep going as i have seen many patients as late responders.early switches renders the patient resistant to many anti-psychotics which might not be true otherwise
  4. Thanks for the comments. I certainly understand that. Having said that, I also practice in the US and have managed to keep patients on the same antipsychotic for 16 weeks with good results. Although, it’s much easier to do with outpatients. With inpatients, the hope is that they will have some response so they can be discharged. They can later on continue the full 16 week treatment as outpatients.
  5. That would make sense if an alternate treatment would be definitely more effective, but in my experience, and based on research data, some people do better by staying in the same antipsychotic if you keep them long enough, as opposed to an early switch, which could create more side effects and may not bring any added efficacy. In reality, we needed more studies looking at that specific issue.
  6. A first episode, with anti psychotics very early, may be masking a Brief Psychosis or a Schizophreniform Disorder or Depersonalization Disorder.
  7. I concur with the gradual titration over several weeks. However, as many of our colleagues say, it is practically impossible because the owners of the business, i.e., the insurance companies do not allow it.
  8. Interesting idea. Did you titrate up the dose, maintain or decrease the dose during the period of 16 weeks?
    When you selected the antipsychotics on pts who had failed initial treatment- was there a specific antipsychotic selected and if not- did all the antipsychotics show the same benefit. How did you deal with the side effects- ex weight gain that would happen with/without symptom improvement.
    If you are getting first episode pts discharged from inpt units who are on high doses of antipsychotics- easier to decrease the meds over a period of 4 months rather than keep increasing the same medication over 4 months.
    Finally, how are you attributing all the changes to the medication rather than the natural course of 4 months on any antipsychotic.
  9. trained years ago at LIJ, the 4-6 week mark is when we would ask: to stick or switch? when you hang in there for 16 weeks, what are you usually seeing at that 4-6 week mark? knowing would be useful.
  10. What happens if no improvement after 16 weeks? Again another 16 weeks with another drug?
    I think we should aim at symptom reduction at the earliest

  11. We use a flexible titration schedule based on symptom response and tolerability. Our data comes from a study (see references: Gallego et al 2011) using risperidone or olanzapine. Furthermore, we are currently using the same approach in a study with risperidone or aripiprazole with positive results. I don’t think that this effect is specific to any antipsychotic and could be applied at least to olanzapine, risperidone and aripiprazole, based on our data. The best way to deal with side effects is to choose the right agent to prevent them (that’s why we rarely use olanzapine as a first line) and to go slow in the dose titration, which would increase the chances of a lower dose at endpoint.
  12. At the 4-6 week mark you would see a 20-30 percentage of patients achieving treatment response. At the 16 week mark , the percent of responders is much higher (60-65%). See Gallego et al 2011 in references
  13. Yes. After our subjects fail the first antipsychotic for 16 weeks, they go for a trial of a second antipsychotic for another 16 weeks. After failing two 16-week trials, they go to clozapine.
  14. I share to concern of poor treatment of insured patients. I can keep an uninsured patient for two weeks if not reponding but i have to justify for fifteen minutes every other day to another money driven professional about continued treawtment and they always win the argument because they are paid to win and i loose loose in time money and quality of care
  15. Can we see what percentage of non-responders at 4th week are responders at 16th week, the percentage to necessitate the continuation or discontinuation? and what percentage are still not responding?
  16. Interesting approach. I look forward to more data from your work. We need much more information about dose ranging and knowledge of variables that affect response to a given molecule and the timing of that response.
  17. I would need to go back to the data to give you the exact numbers. In the mean time, I can say that 22% of the patients responded by week 4 and 65% responded by week 16, using stringent response criteria.
  18. I am a patient who received ETC in 2007. I was to have 16 sessions but I asked the dr. for 20 since I thought more=less depression. The ECT effect was short lived- less than a month. Instead I suffered memory loss and ongoing memory problems that still plague me to this day. I would never suggest ECT to any patient as it is not safe. I made a terrible decision and would like to warn others to say no to psychiatrists who suggest ECT.
  19. I agree that ECT has to be used only for the cases which do not respond to long term treatment and where the symptoms are dangerous for the patient. I had two cases of patients with sch who responded very well to ECT. Memory loss after ECT – we treated once with neurofeedback and suceeded to get good results.

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