Antipsychotics Should Be Used for Non-Psychotic Depression Treatment

Antipsychotics Should Be Used for Non-Psychotic Depression Treatment

While some disagree, it’s important that people understand that antipsychotics need to be used for non-psychotic depression treatment, when appropriate.

At any one time, 14 million people suffer from depression but only 60-70% of these people respond to antidepressant treatment. Of those who do not respond, 10-30% exhibit treatment-resistant symptoms including “difficulties in social and occupational function, decline of physical health, suicidal thoughts, and increased health care utilization.” Treating these people presents a huge issue for healthcare practitioners and one of the options they consider is the use of a medication class known as antipsychotics.

Recently, a group called the Therapeutics Initiative wrote a letter entitled Antipsychotics should not be used for non-psychotic depression. Their conclusions are as the title suggests: this body found little evidence to support the use of antipsychotics in the treatment of non-psychotic major depressive disorder.

And while I respect the work of this body and while they have considered some evidence (in the case of quetiapine [Seroquel], an antipsychotic), there is more to consider on the issue.

Conclusions of the Therapeutics Initiative on Antipsychotics and Depression

Their conclusions are as follows (bold theirs):

  • Quetiapine has not been shown to improve overall function as monotherapy or when added to an antidepressant for unresponsive major depressive disorder.
  • There is insufficient scientific evidence that quetiapine reduces any depression-rating scores. Quetiapine causes sedation, which improves sleep.
  • Biased trial methodology exaggerates any apparent benefits, and minimizes disadvantages such as weight gain or other long-term harms.
  • Adverse effects include frequent sedation, anticholinergic effects and weight gain. Long-term harms are unknown, but likely include elevated cardiovascular risk related to weight gain and metabolic changes.
  • Evidence for other antipsychotics for depression is not better.

Note that these conclusions were based on their review of studies featuring quetiapine only and they are generalizing those conclusions with regards to other antipsychotics. This generalization is particularly harmful in the case of aripiprazole (Abilify) as it is Food and Drug Administration approved for use as an adjunctive treatment (treatment alongside an antidepressant) in depression.

But let’s look at some of the recent studies that didn’t make it onto the radar of the Therapeutics Initiative.

Evidence for the Use of Antipsychotics in Non-Psychotic Depression

In a 2014 analysis by Ozaki et al in Psychiatric and Clinical Neurosciences, the efficacy of aripiprazole augmentation to treat major depressive disorder was reviewed in approximately 600 patients who had inadequate response to antidepressant treatment alone. In the analysis, it was found that aripiprazole produced consistently greater improvements in depression symptoms and that this improvement could not be attributed to other factors such as the type of antidepressant used. Additionally:

Compared to placebo, aripiprazole resulted in significant and rapid improvement on seven of the 10 MADRS [a depression rating scale] items, including sadness.

In 2014, an analysis by Stewart et al in the Journal of Affective Disorders reviewed the results of three randomized, double-blind, placebo-controlled trials of adjunctive aripiprazole in adults with major depressive disorder and inadequate response to one-to-three antidepressant trials. It was found that when aripiprazole was combined with an antidepressant, it was superior to placebo in cases of mild, moderate and severe depression with the most effect seen in severe depression. Common side effects included akathisia and restlessness.

Additionally, in 2015, The Journal of Psychiatric Research published a study on the difference between switching antidepressants and adding aripiprazole in 101 patients with major depressive disorder. It was found that those who had aripiprazole had much better clinical outcomes than those who switched antidepressants. Positive response to the treatment with the antipsychotic was found in 60% of patients and in only 32.6% of antidepressant switchers and 54% of patients on the antipsychotic met the criteria for depression remission whereas only 19.6% of those on the antidepressant switch met the same criteria.

In short, plenty of evidence contradicting the Therapeutics Initiatives view (at least showing that their views on quetiapine do not warrant generalization) that antipsychotics en masse should not be used to treat non-psychotic depression exists. And while any one of these studies are certainly not definitive, taken as a whole, the evidence warrants serious consideration for those who are not responding to traditional treatment with antidepressants.

What Happens When Treating Depression with Antidepressants Fails?

Keep in mind here, these studies are done on people who have not gotten better on antidepressants alone — often more than one time. In other words, these patients have fewer and fewer options as more and more antidepressants fail them.

So what of them? What of the actual people behind the data? What do you do if you don’t respond to antidepressants but antipsychotics are taken off the table in spite of evidence that they should not be?

Well, there aren’t many options left for you if antidepressants aren’t working and you’re severely depressed. One thing you could try is electroconvulsive therapy (ECT). ECT has a side effect profile that often includes amnesia and many are hesitant to try it for a variety of reasons that are beyond the scope of this article.

Then there are the treatments of vagus nerve stimulation (which requires surgery) and repetitive transcranial magnetic stimulation. One of those might work if you have tens-of-thousands-of-dollars to throw around (as they’re often not covered by insurance).

And then that’s it. Done. Still sick? Too bad for you. (Here I am assuming that you have also investigated psychotherapy for depression – something else many insurance companies will pay little for.)

The Patient Perspective on Antipsychotics to Treat Depression

So, if you’re a patient, what do you do? I’ll tell you what you do, you plead with your doctor not to take the opinion of a handful of doctors who have clearly not reviewed all the evidence and beg your doctor to add an antipsychotic into the mix. That antipsychotic might not be quetiapine (many of their criticisms of it are valid) but you need something. You need a new class of medication because the existing ones aren’t working for you.

And let’s say the Initiative is right — that quetiapine only works modestly better than a placebo. Okay, if you were the patient with no options, would you prefer to try something with little possibility of usefulness or nothing at all? What if you were his or her parent? Or sibling? Then what would you prefer that person do?

My point here is this: when we talk about adjunctive quetiapine and aripiprazole we’re talking about medications that have met the standards of efficacy set forth by the Food and Drug Administration in the treatment of major depressive disorder. We’re talking about real, live options for people that can be very, very sick. And the only reason that a doctor would dare come out and tell other doctors not to try an approved and evidence-based treatment is because we’re dealing with a “mental” illness here. For some reason, those of us with mental illness are treated less seriously and our wellbeing is less important than those with other diseases. Let’s see doctors try to ignore an approved treatment for cancer patients because the side effect profile is adverse. You know what’s adverse? Not being able to get out of bed and feed yourself. You know what’s adverse? Dying by suicide. We’re not talking about a little sadness here. Those things are as severe as any illness can get.

And the shame of it is that many general practitioners (family doctors — not psychiatrists) will read this letter and think that the issue is cut and dried. It isn’t. It’s far from it. Psychiatrists in actual practice with actual patients could tell you that. And patients – those that have been saved by antipsychotics and others – could tell you that, too. But it seems, no one is listening.

Banner image By Linda Bartlett (photographer) [Public domain], via Wikimedia Commons.

Image by Housed (Own work) [CC BY-SA 3.0], via Wikimedia Commons.


About Natasha Tracy

Natasha Tracy is an award-winning writer, speaker and consultant from the Pacific Northwest. She has been living with bipolar disorder for 18 years and has written more than 1000 articles on the subject.

Natasha’s New Book

Find more of Natasha’s work in her new book: Lost Marbles: Insights into My Life with Depression & Bipolar. Media inquiries can be emailed here.

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