Do Psychiatric Drugs Take Weeks to Work?

If you've been told by your doctor that antidepressants and antipsychotics take weeks to work, you've been told a myth, and your health care provider clearly either hasn't looked at the actual data for these drugs, or doesn't believe the data.

Alex J. Mitchell, The British Journal of Psychiatry (2006) 188: 105-106, mentions three studies in which effects of antidepressants were measured on short time scales. These were all fairly sizable studies, with 369, 429, or 1,277 patients. In one of the studies, researchers "found that regardless of which antidepressant the patient was taking, there was a measurable early effect on day 1." (Emphasis added.) "By day 3, 20% of patients had shown some improvement, and by day 7 50% had improved. Furthermore, 90% of those who showed any response during the first 3 weeks went on to become full responders. Drug–placebo differences (where apparent) could be detected as early as day 5." In another study, "Patients were requested to complete a self-report mood rating every third day. All patients showed a decrease in depression (and anxiety) within the first 3 days, but with little further improvement in non-responders from days 4 to 6."

The following graph, from Kornstein et al. (2009), shows response data, pooled from four studies, for Lexapro (escitalopram; an SSRI) versus a variety of SNRIs. Patient outcomes were measured using the Montgomery–Åsberg Depression Rating Scale (MADRS). Note the asterisk under the first red square, indicating statistical significance, which occurs at Week 1.

These sorts of graphs are not hard to find and your clinician should be familiar with them. Yet, most psychiatrists and nurse practitioners continue to propagate the myth (and it is just that: a myth) that antidepressants (when they work, which isn't always the case, for all patients) take weeks to show any effect. Certainly, it can take many days for some of these drugs to reach steady-state concentrations in tissues, but the behavioral and mood effects, when they happen, are measurable in as little as one to three days (see Mitchell, referenced above).

The following graph shows that Abilify works for agitation symptoms in as little as 30 minutes (when administered intramuscularly).

Intramuscular Abilify (aripiprazole) causes a reduction in agitation in as little as 30 minutes, although statistical significance is not achieved until 60 minutes (45 miutes for Haldol). From Andrezina et al. (2006), Psychopharmacology 188:3, 281-292.

This is obviously a different situation than depression, but the point is, behavioral effects don't take weeks to occur with these drugs. (Note: Abilify is approved for irritability in autism, treatment of psychosis in schizophrenia, and treatment of depression in an adjunctive capacity.) Abilify, when given intramuscularly in a hospital setting, begins to have measurable effects on behavior in minutes, even though the drug has an incredibly long half-life (50+ hours, or up to 90+ hours for certain metabolites). Abilify is not unique in this respect. Graphs similar to the one above can be found for other antipsychotics here.

So the next time anybody tells you these drugs take weeks to work, understand that you're dealing with someone who either hasn't read or doesn't believe the literature. The literature says effects happen almost as soon as you start to look for them.

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Is Abilify Effective for Depression?

Abilify is the top-selling prescription drug in the U.S., a ranking it has held for a couple of years now. What's astonishing is that this drug was originally approved as (and only used as) an antipsychotic. My wife, who has schizoaffective disorder, is an experienced user of Abilify, Haldol, Latuda, Zyprexa, and Saprhis. She will attest to the antipsychotic properties of Abilify (and I'll show a graph for efficacy further below). But treatment of psychosis is not what made Abilify the top-selling drug in the U.S. Abilify is now widely prescribed as an adjunctive drug for depression; plus other uses, both on-label and off-label.

The manufacturer says Abilify is indicated for:

• Use as an add-on treatment to an antidepressant for adults with Major Depressive Disorder who have had an inadequate response to antidepressant therapy
• Treatment of manic or mixed episodes associated with Bipolar I Disorder in adults and in pediatric patients 10 to 17 years of age
• Treatment of schizophrenia in adults and in adolescents 13 to 17 years of age
• Treatment of irritability associated with Autistic Disorder in pediatric patients 6 to 17 years of age

Physicians and consumers alike have bought into the "Abilify as an adjunct" idea in a big way. Why has this "adjunct" modality become so popular? The main reason is that regular antidepressants simply aren't very effective, and people in a desperate mental state naturally want to know what else can be done other than switching from one ineffective drug to another.

But how good is Abilify, really, as an adjunct to antidepressants? Here is the graph touted on the Abilify website:

Abilify's efficacy (as an adjunct to antidepressants), versus placebo. (Click to enlarge.) The vertical scale plots average change (decrease) in patient scores on the Montgomery–Åsberg Depression Rating Scale.

This graph pools data from three studies. It shows that the average drop in MADRS score for patients on placebo-plus-antidepressant is a drop of 6.2 points after 6 weeks (from a starting average score of 26). When Abilify is added to the mix, the average score drop is 9.4 points. So if you add Abilify, you can expect a 3.2-point drop in your MADRS score that you wouldn't otherwise have had.

But if you look at the MADRS test, a change in just one answer (e.g., better sleep) could easily produce a 3-point change in your score. What you need to ask yourself is whether this magnitude of change is clinically significant. If you found a dollar bill on the sidewalk, your MADRS score would probably change by 3 points (briefly, of course). If your tax refund was $100 larger than you expected, it would probably mean a 3-point change on MADRS. The point is, the magnitude of change we're talking about here is small. It may be statistically significant, but is it clinically significant?

Abilify's primary use is in treatment of schizophrenia symptoms. Here's the efficacy graph for improvement on the PANSS scale, a common rating system for assessing schizophrenia symptoms:

Abilify efficacy with respect to schizophrenia symptoms (placebo in grey).

This is a much different graph. It shows what anyone would call good separation from placebo: five to eight times bigger change, with Abilify, than with placebo alone.

Abilify costs over a thousand dollars a month (10 mg, 30 pills) if you were to have to pay for it out of pocket. For most patients, this cost is hidden by insurance (or Medicare, in my wife's case). If you were taking Abilify for depression (as an adjunct) and had to pay for it out of pocket, you'd probably find the cost depressing (to the tune of much more than a 3-point drop in MADRS). Still, desperate people will do desperate things. Adding Abilify is "one more thing to try." So by all means try it. But don't expect miracles. If you see any effect at all, it's likely to be a rather small one.

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