Question from a Member:
Is there data about the risk of tardive dyskinesia with prolonged use (years) of LOW-dose aripiprazole?
Why is this question important?
I think you will agree that our colleague asks a very clinically relevant question because:
1. Relatively low doses of aripiprazole are commonly added to antidepressant medications after an inadequate response to the antidepressant alone for the treatment of major depressive disorder (MDD).
2. Despite so many years of experience with this, there is no guidance at all about how long to continue aripiprazole (or another antipsychotic) if it is effective as an adjunct to a conventional antidepressant for the treatment of major depressive disorder.
In practice, patients with major depressive disorder whose illness responds to antipsychotic “augmentation” of a conventional antidepressant typically stay on the antipsychotic for fairly long periods of time. Weight gain and tardive dyskinesia are important risks of long-term treatment with aripiprazole.
Why don’t we have more straightforward answers?
You may legitimately wonder why published research doesn’t provide us with straightforward answers to questions about the risk of tardive dyskinesia (TD). There are many reasons for this, including the following:
Other possible explanations for the TD
1. The incidence of new-onset TD depends on many risk factors other than the antipsychotic treatments received. These include both patient-related (for example, older age) and illness-related (for example, mood disorders).
2. The incidence of new-onset TD also depends on that particular patient’s vulnerability to developing TD, possibly due to genetic factors.
Time to onset of TD
1. Since the risk of developing TD increases with time, at least in the first few years, answering questions about the risk of TD requires research studies involving long-term follow-up, which are harder to do.
2. In almost all long-term studies, the proportion of patients who stop participating increases over time.
Early and mild TD is hard to diagnose and often missed
1. The onset of TD is typically gradual.
2. TD typically varies in severity from day to day, depending, in part, on how anxious the person is.
3. The movements of TD, being intermittent and irregular, are easily confused with normal movements. So, the diagnosis of early TD is often missed.
4. TD tends to be masked by ongoing antipsychotic treatment.
5. TD movements often decrease, at least temporarily, if:
– The antipsychotic dose is increased, or
– The patient is switched to an antipsychotic with stronger D2 receptor–blocking activity.
Next, let’s look at what we do know about aripiprazole and TD despite the challenges of research about tardive dyskinesia (TD).
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