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Atypical Antipsychotics: The Need-to-Know Series (“Should you?”)

Atypical Antipsychotic

“Okay, I’m at least comfortable with what the atypical antipsychotics are. But I still don’t understand why I should take them with my antidepressant. I need to know more.”

The atypical antipsychotics – Zyprexa, Risperdal, Seroquel, Abilify, Geodon, Invega, and more – are powerful medications. When prescribed correctly, their rewards can be great. But their side effects are ever-treacherous.

We started our atypical antipsychotics need-to-know series yesterday with some foundational info. Here’s a link to Part 1.

Let’s wrap things up today by chatting about why the atypicals are used as add-ons to antidepressant therapy. And I’ll even toss in a few opinions, including how I feel about prescribing atypicals to children and adolescents.

“Why should I use an atypical antipsychotic with my antidepressant?”

Likely, no one has to tell you – major depressive disorder is tough to treat. Given that reality, augmentation (add-on) therapy is nothing new.

Decades ago, the first generation antipsychotics were used as add-ons. But that ended when the atypicals, with supposedly fewer side effects, made the scene.

You’d have thought it was manna from heaven. Olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), aripiprazole (Abilify), zaprasidone (Geodon) – they were all used.

And in many cases the strategy worked. Still does.

In fact, in 2008 aripiprazole (Abilify) became the first atypical antipsychotic – first med of any kind – approved by the US Food and Drug Administration (FDA) for use as an augmentation agent (in the treatment of major depressive disorder).

But with antipsychotics, it always comes down to the side effects – and the atypicals still bring them. And that’s why so many stop taking them.

“Why do atypicals work as add-ons?”

First of all, don’t ever kid yourself. There’s a whole lot of bio-babble behind why atypicals supposedly work as add-ons. But I’m here to tell you no one truly understands the very bottom-line why’s.

Here, how ’bout this load: 5-HT2 receptor antagonists, 5-HT1A receptor partial agonists, dopamine D2 receptor affinity, norepinephrine reuptake transporter moderate affinity, dopamine, serotonin, norepinephrine transporters, and on and on.

But let’s go ahead and take a look at one example and see if we can make sense of it. Okay, we learned that aripiprazole (Abilify) has been FDA approved for major depressive disorder augmentation therapy. One of its actions is as a 5-HT1A receptor partial agonist.

A common and troubling characteristic of any serotonin-influencing med (like the SSRIs) is something known as therapeutic lag. Simply, it can take some time for them to work.

5-HT1A receptor partial agonists help with therapeutic lag. So if an antidepressant treatment regimen can grab some 5-HT1A receptor partial agonist action, quicker relief and greater overall efficacy will be realized.

Again, aripiprazole (Abilify) works as a 5-HT1A receptor partial agonist.

By the way, a brand new antidepressant, Viibryd (vilazodone), will soon be on pharmacy shelves. It’s an SSRI/5-HT1A receptor partial agonist combo! Here’s a link to a piece I did on Viibryd.

Pediatric and Adolescent Use

I continue to be stunned at how frequently the atypicals are prescribed for children and adolescents. I’ve worked with seven-year-olds who had aripiprazole (Abilify) on their meds roster.

I am not naive. I’m fully aware of the upsetting and dangerous behaviors with which children and adolescents are presenting these days. (Actually, it breaks my heart.)

I have no problem with prescribing atypicals for children and adolescents in the midst of psychotic or manic circumstances. But it’s my opinion atypicals are all too often being prescribed as quick-and-easy behavior remedies. And not only is it wrong, in  my heart and mind it’s just “this much” short of being criminal.

Stop and think about the extrapyramidal side effects of the atypicals – tardive dyskinesia. What are these kids going to be enduring decades from now?

Some Thoughts and a Close

The atypical antipsychotics are sophisticated and powerful medications. And they’re indicated and efficacious for so many difficult psychiatric situations.

However, I truly believe – just like the SSRIs – they were over-hyped when they arrived. And every day seemingly brings more evidence they aren’t the minimal-side-effect miracle workers they were supposed to be – at least for non-psychotic situations.

Don’t be so naive as to believe Big-Pharma hasn’t been – and isn’t – motivated by profits in all of this. As we learned in yesterday’s piece, worldwide sales of all antipsychotics in 2008 were $22 billion. And the average cost of an atypical prescription is four-times higher than a first generation antipsychotic.

Things that make you go, “Hmmm…”

So how do you feel about the atypical antipsychotics? Any experiences you’d like to share?

Your comments rule!

  • Russianguy25

    “By the way, a brand new antidepressant, Viibryd (vilazodone), will soon be on pharmacy shelves. It’s an SSRI/5-HT1A receptor partial agonist combo! Here’s a link to a piece I did on Viibryd”… so it’s an anti-psychotic and an anti-depressant?

  • The 5HT1A receptor is an inhibitive autoreceptor. That is, it’s on the presynaptic terminal, and when agonized (stimulated) it slows the release of serotonin from the presynaptic (sending) nerve. So however this medication is working, it isn’t by increasing serotonin release or by keeping serotonin in the synapse.

    • Thanks for your visit and comment, Sonya. I’ll do some more digging and see if I can come up with more insight…

  • dmwritt

    Hi, I just found this blog searching for information about Viibryd.  I have battled disabling depression and mood swings for 15+ years.  My diagnosis has changed numerous times over the years despite a relatively consistent core of care-providers (primary, psychiatrist, therapist, endocrinologist…).  The problem: nothing has worked consistently and some things have worked completely contrary to what was anticipated.  (So you know, substance abuse or starting or stopping meds without doctor supervision has never been an issue for me, thankfully.)  Atypical antipsychotics are an example.  Although, I am almost certain I have some type of “soft” bipolar–without stereotypical mania (no psychotic episodes, mild or otherwise) or hypomania (no days without sleep or over-the-top sex or spending bends), rather, a mixed and mild agitation/anxiety that punctuates my depression unexpectedly.  After years without success from a number of anti-depressants (before bipolar was even considered) I tried Zyprexa.  Within a couple weeks, I suddenly (out-of-the-blue) tried to kill myself, something I had never done or considered doing before (even in deepest depression)… it was a sudden panic I cannot describe.  I stopped taking the Zyprexa after being hospitalized, but not because I or my doctors thought it contributed to the episode.  The medication was forgotten for years (and the class of medications to which it belonged never raised red flags on my radar).  Years later, after I had been tentatively diagnosed with bipolar, but had had no success with lithium or Depakote (and related medications), I was put on Rhisperdal.  Quickly, I become nearly (although, not classically) “psychotic”.  This time, the medication was considered a possible contributing factor and we discontinued it.  However, no connection was made to the class of medications (atypical antipsychotics) or the sudden panicky “suicidal” episode I had experienced years before (this could be attributed, in part, to the fact that my care team had changed in those intervening years because I had moved from Florida to Kansas).  Within the year, I was put back on Zyprexa (having completely forgotten ever taking it before).  Again, within a couple of weeks, I suddenly and without warning tried to kill myself (this was only the second time in my history that I had done this).  That was when we all started to realize something was amiss.  After carefully reviewing my history, I came to realize that the feelings I was experiencing (the “panic”) sounded more like symptoms of severe dopamine deficiency, and the anxiety and agitation that had led up to my starting these medications, although, in some ways resembling ensuing mixed-state hypomania brought about by too much dopamine, felt (internally) more like detailed descriptions of dopamine depletion (panic growing from a feeling of being “boxed-in” by a stuck brain, unable to get from point A to point B in your head, etc.)… it made sense that if I treated dopamine depletion with a medication designed to decrease dopamine even more that I would react precisely as I did.  I have never touched atypicals again (although I did try a LOW dose of Abilify at one point– to increase, not decrease dopamine– with no effect).  Clearly, mine is not the typical reaction, so I do not blanket discount that they can benefit someone who really does need it, but I would warn people to consider that sometimes a duck is NOT a duck– some people can exhibit behaviors that resemble others, but for very different neurophysiological reasons.  That said, I do not have an answer for what to do in a case like mine.  My doctors and I have been searching for years without success. 
    This entry, I suppose, serves as (1) a warning to others to try things faithfully (with a doctor) but never stop considering that the obvious answer may not be the first one that comes to everyone’s mind, and (2) a plea for help from anyone else (doctor or patient) who has experienced similar phenomena and found any success in management. 
    P.S. I do continue to take Lamictal with my other meds (which include antidepressants, anti-anxiety, and Adderall– the best combination I found thus far) just to be “safe” with respect to the possible bipolar aspect of my illness, but I have never experienced heightened mania-type episodes related to the drugs you’d think would bring those on (antidepressants and Adderall).  My mood-changes seem to have remained the same over the last fifteen years (even though the dopamine enhancing drugs only began a few years ago). The Adderal just improved my overall energy, concentration, and sense of calm; nonetheless, I remain disabled by my recurring depression, anxiety, and irregular functionality.

    • Hi dmwritt…

      Appreciate your very detailed comment. It’s participation like yours that holds the potential to help so many.

      Please continue to visit and post…


  • hanni

    I made a massive mistake taking risperidone with an anti depressant. Two years after I stopped taking it I cannot enjoy anything. I feel dead insidea I feel very much less intelligent than how I was before. Im completely different.
    I wish I had died instead of taking risperidone rather than be left to live in such a diminished way. So what they make you live – for what – with no ability to feel.

    • Hey, Hanni!
      Glad you stopped-on-by and commented. So sorry you’ve had a rough go with risperiodone. I can’t imagine what it would be like to feel “dead inside.” Atypicals – so many psychotropics, for that matter – are very dicey business. It just throttles me when I see the ads on TV for antidepressant augmentation with atypicals. Yes, I suppose in very difficult cases the regimen may be indicated, but the ads come off as if it’s no big deal.
      Best to you, Hanni. I’m hoping things turn around for you…