When Shorter Is Better

We know a lot about when to start medications but little about when to stop them. In this article, I’ll highlight treatments that are best started with an endpoint in mind.

Antidepressants

Long-term antidepressant use is on the rise, but in some situations a briefer course is ideal. Specifically, patients who have had fewer than three episodes can usually taper off their antidepressant after six months of recovery. Waiting longer does not confer additional benefits, but coming off before the six-month mark raises the risk of relapse by up to 11-fold (Baldessarini RJ et al, J Clin Psychopharmacol 2015;35(1):75–76). When stopping the antidepressant, a slow taper over two to four weeks prevents relapse better than abrupt discontinuation. An even longer taper, such as over three to 18 months, is sometimes necessary when the patient has been on the medication for many years or has problematic withdrawal symptoms.

For recurrent depression, antidepressants have preventative effects, but psychotherapy may have even more. In a recent network meta-analysis, psychotherapy increased the odds of sustained remission from depression 1.5-fold over pharmacotherapy (Furukawa TA et al, World Psychiatry 2021;20(3):387–396).

The preventative promise of psychotherapy is the inspiration behind the sequential treatment approach, which starts with an antidepressant for acute symptom relief. If the patient responds, they are kept on the antidepressant for another three months, at which point the medication is tapered while an active form of psychotherapy is added (eg, cognitive behavioral therapy [CBT], mindfulness-based CBT, or well-being therapy). This sequential treatment approach prevented depression as effectively as antidepressant continuation in 11 randomized controlled trials (Guidi J and Fava GA, JAMA Psychiatry 2021;78(3):261–269).

Exercise is another effective pathway for prevention. In a randomized trial from Duke, aerobic exercise and sertraline had similar antidepressant effects after four months, but only exercise was successful at preventing depression 10 months later, with relapse rates of 8% for exercise vs 38% for sertraline (Babyak M et al, Psychosom Med 2000;62(5):633–638).

If therapy and exercise are not feasible, the best course is usually to continue the antidepressant in patients who’ve had at least three past episodes. Continuation is not bulletproof, but it reduces the relapse risk from 40% to 20% over a follow-up period of six to 12 months, according to a meta-analysis of 40 trials (Kato M et al, Mol Psychiatry 2021;26(1):118–133).

Antidepressant augmentation

Antidepressant adjuncts like lithium and the antipsychotics carry long-term risks that make time-limited treatment desirable. Research in this area is scant, but studies on the topic suggest that patients need at least three months of recovery before stopping these agents. Most experts wait longer—at least six months—mirroring the time course for standard antidepressant continuation.

In my own practice, about 40% of patients are able to taper from adjunctive therapies after six months but another 60% are not. Sometimes there is good reason to continue the augmentation besides episode prevention. Lithium, for example, has robust antisuicide effects, and the risk of suicide rises in the first month after lithium is stopped (Song J et al, Am J Psychiatry 2017;174(8):795–802). A slow taper—over at least two weeks and preferably several months—is necessary when discontinuing lithium to prevent rebound mood episodes (Baldessarini RJ et al, Bipolar Disord 2022;24(7):720–725).

Antimanic augmentation

Antipsychotics are also added to mood stabilizers to treat breakthrough mania, and here we have greater clarity on how long to continue the adjunct. An independently funded study randomized 159 patients who had recovered from mania with risperidone or olanzapine augmentation to either remain on the antipsychotic or switch to a placebo after a brief period of recovery (two to three weeks) or a longer period (six months). Early discontinuation led to higher relapse rates, but continuation beyond six months offered no protective benefits over placebo (Yatham LN et al, Mol Psychiatry 2016;21(8):1050–1056).

Hypnotics in depression

Patients with depression often remain on a hypnotic long term, but a recent study suggests they may be able to stop the hypnotic after their depression has resolved. The study began by randomizing patients with major depression and insomnia to either zolpidem CR (Ambien CR) or a placebo for sleep while simultaneously starting them on an SSRI. The patients were advised from the start that the sleep medication would only be temporary and would be abruptly stopped at the end of the trial.

As expected, patients slept better on zolpidem, but the surprise came at the end of the two-month trial when the hypnotic (or placebo) was abruptly stopped. Sleep did not worsen, and in fact it continued to improve off the zolpidem (McCall WV et al, Am J Psychiatry 2019;176(11):957–965).

This benefit may be unique to depression, as it was not seen in trials of primary insomnia or generalized anxiety disorder with insomnia. In those conditions, patients gradually lost some—but not all—of the gains in sleep after the z-hypnotic was discontinued. However, they did not “rebound” with acute worsening of insomnia, offering some reassurance that z-hypnotics do not have significant withdrawal effects (Ancoli-Israel S et al, Sleep 2010;33(2):225–234).

Putting it into practice

There are many other scenarios where time-limited treatment is ideal. The prevalence of anxiety disorders goes down after age 60, allowing a potential taper of anxiolytic medications. Likewise, adolescents may grow out of ADHD as they enter adulthood, although new studies suggest the symptoms are more likely to wax and wane than fully resolve in adulthood (Sibley MH et al, Am J Psychiatry 2022;179(2):142–151).

Medication side effects may improve over time, allowing cessation of antidotes like propranolol or benztropine. On the other hand, some side effects get worse in old age, shifting the risk-benefit balance in favor of deprescribing the causative med. Examples include tardive dyskinesia, anticholinergic effects, fall risks, and—with serotonergic antidepressants—osteopenia.

In practice, time-limited treatment encounters numerous obstacles. Patients may have a psychological attachment to the medication. They may experience withdrawal effects that they confuse with relapse, or the drug may have rewarding properties that they confuse with therapeutic effects (particularly with benzodiazepines, z-hypnotics, and stimulants). To increase the chance of success, try the following:

1. Set up the expectation of a short-term trial from the start.
2. Pair the treatment with behavioral changes that can prevent relapse, such as exercise or psychotherapy. Start hypnotics with a behavioral program like CBT for insomnia, which is available through self-guided apps like Somryst or CBT-i Coach (see TCPR March 2022).
3. Taper the medication slowly, over at least two weeks, and preferably longer for medications with known withdrawal problems like lithium, benzodiazepines, and serotonergic antidepressants.

CARLAT VERDICT 

Medications that get patients well are not always necessary to keep them well. Look for situations where time-limited treatment can do the job, particularly with adjunctive therapies, hypnotics, and time-limited disorders like nonrecurrent major depression.