A Psychiatrist at Large

The brain, behavior, and everything in between.

Newer Is Not Always Better

To switch or not to switch? This is the question.

haloperidol injection
haloperidol injection solution
We hear a lot about the benefits of second generation or atypical antipsychotics when compared to the older, first generation antipsychotics for the treatment of schizophrenia.

The class of the atypical neuroleptics has been gradually expanding over the last almost two decades.

In this country, FDA approve clozapine (Clozaril) for treatment-resistant schizophrenia in 1989.

In 1993 risperidone (Risperdal) was the first atypical of what turned out to be a long series of new medications approved for the treatment of schizophrenia. Olanzapine (Zyprexa), ziprazidone (Geodon), aripiprazole (Abilify), quetiapine (Seroquel), paliperidone (Invega), iloperidone (Fanapt), asenapine (Saphris), and lurazidone (Latuda) followed suit and completed the rank of the burgeoning atypical class.

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These medications gained clinical prominence based on a perceived advantage in terms of cognitive effects and improvement in the negative symptoms of schizophrenia, as well as better overall tolerability (meaning less adverse effects) when compared to their older colleagues, such as haloperidol (Haldol) and chlorpromazine (Thorazine).

Unfortunately, after a preliminary wave of excitement, later data did not substantiate the cognitive benefit advantage of the newer class. Also, while tolerability for some adverse effects was better with the newer meds (specifically for the extrapyramidal or Parkinson like type of problems), quite a few members of the new class came to be responsible for a tide of metabolic problems in patients with schizophrenia.

To summarize: when it comes to substantiating clear advantages of the newer meds the evidence is ambiguous. What it’s clear though is that the price of a prescription of any atypical runs into the hundreds of dollars a month compared to about $20 for a month supply of generic haloperidol.

At the same time, due to the long term neurological effects of the older meds, clinical guidelines, which value safety above everything else, generally recommend second generation medications to be used as first line treatments for schizophrenia. Second comes first and first (generation) goes second.

Further, due to the perceived benefits of the newer meds, clinicians tend to routinely switch patients from the older to the newer drugs.

Which brings me to the point of this post.

A new study by Covell et al indicates that patients maintained on long acting haloperidol and fluphenazine(another older drug) injections when switched to Consta ( risperdone long acting) injections tended to discontinue their new medication faster than the patients who were simply continued on their original medication. Interestingly, the switching did not change reports of psychopathology, hospitalizations, or neurological adverse effects, meaning things did not get worse, but also (and a thumbs down for risperidone), they did not get better either. In fact, the “switched” ended up with somewhat higher body mass and increased prolactin, than the patients who stayed on their original meds (another thumbs down for risperidone). Furthermore, and this really is the main finding of this study, the rate of discontinuation, assessed during a six month follow up period, was higher for the patients who got switched.

It is really not that clear why the difference in discontinuation. However, what we know is that when schizophrenia patients stop taking their medication they greatly increase their risk to relapse.

Clearly not a good thing.

My conclusion?

Newer is not always better. Specifically, when it comes to patients with schizophrenia who are stable on their meds (even the older and not that fancy sounding meds), it might be better to stay the course rather than “automatically” switching to the newest drug on the block.

References:

Covell NH, McEvoy JP, Schooler NR, Stroup TS, Jackson CT, Rojas IA, Essock SM; for the Schizophrenia Trials Network. Effectiveness of switching from long-acting injectable fluphenazine or haloperidol decanoate to long-acting injectable risperidone microspheres: an open-label, randomized controlled trial. J Clin Psychiatry. 2012 Mar 6. [Epub ahead of print]

 

Adrian Preda, M.D., is an Associate Professor of Psychiatry and Human Behavior at the UC Irvine School of Medicine.

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