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

“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!