Discontinuing psychotropic drug treatment

Background: Stopping antidepressants is often difficult due to withdrawal. Taperingstrips were developed to facilitate antidepressant discontinuation according to the recently described Horowitz-Taylor method, allowing for personalised titration of discontinuation to the intensity of withdrawal. A taperingstrip consists of antidepressant or other medication, packaged in a 28-day roll of small daily pouches, each with the same or slightly lower dose than the one before it. We previously reported that the short-term success rate of antidepressant taperingstrips was 71%. Here, we examine longer-term outcome after 1–5 years. Methods: Patients whose doctor had ordered taperingstrips between January 2015 and December 2019 were sent a questionnaire for participation in anonymised research in January 2020. Of 1012, 483 participated, of whom 408 (85%) had attempted antidepressant tapering. Results: Of the 408 patients included, 192 (47%) had used strips for tapering venlafaxine, 142 (35%) for paroxetine and 74 (18%) for other antidepressants. Median length of antidepressant use was 4 years, and most (61%) had tried to come off without taperingstrips at least once. After 1–5 years, 270 patients (66%) remained off antidepressants after tapering their antidepressant, 6 (2%) had successfully reduced their medication, 87 (21%) had restarted due to (self-reported) relapse, 35 had restarted for another indication (9%), and 10 (3%) reported another outcome. People with more severe experience of withdrawal prior to tapering, and people who had been on antidepressants for a shorter period of time, were more likely to remain off medication after 1–5 years. Conclusion: The previously reported 71% short-term success rate of taperingstrips in the most severely affected group, was matched by a 68% rate after 1–5 years. The evidence-based approach of personal tapering to counter withdrawal, as used for drugs causing withdrawal, for example, benzodiazepines, may represent a simple solution for an important antidepressant-related public health problem, without extra costs.

Section: Discussionmentioning

confidence: 99%

Outcome of antidepressant drug discontinuation with taperingstrips after 1–5 years

Groot

2020

“…Therefore, the internal validity of relapse prevention (discontinuation) trials is compromised. 34,46,73 Given that the outcome in these maintenance studies is confounded, we must acknowledge that they are uninterpretable and cannot serve as a valid evidence base for long-term maintenance treatment. The next question hence is whether there is evidence of prophylactic effects from studies with other methodologies that would support long-term antidepressant treatment.…”

Section: Withdrawal Confounding In Relapse Prevention Trialsmentioning

confidence: 99%

How effective are antidepressants for depression over the long term? A critical review of relapse prevention trials and the issue of withdrawal confounding

Hengartner

2020

The aim of this article is to discuss the validity of relapse prevention trials and the issue of withdrawal confounding in these trials. Recommendations for long-term antidepressant treatment are based almost exclusively on discontinuation trials. In these relapse prevention trials, participants with remitted depression are randomised either to have the antidepressant abruptly discontinued and replaced by inert placebo or to continue active treatment. The drug–placebo difference in relapse rates at the end of the maintenance phase is then interpreted as a prophylactic drug effect. These trials consistently produce remarkable benefits for maintenance treatment. However, the internal validity of this trial protocol is compromised, as research has shown that abruptly stopping antidepressants can cause severe withdrawal reactions that lead to (or manifest as) depression relapses. That is, there is substantial withdrawal confounding in discontinuation trials, which renders their findings uninterpretable. It is not clear to what degree the drug–placebo separation in relapse prevention (discontinuation) trials is due to withdrawal reactions, but various estimations suggest that it is presumably the majority. A review of findings based on other methodologies, including real-world long-term effectiveness trials like STAR*D and various naturalistic cohort studies, do not indicate that antidepressants have considerable prophylactic effects. As absence of evidence does not imply evidence of absence, no definitive conclusions can be drawn from the literature. To enable a thorough risk–benefit evaluation, real-world effectiveness trials should not only focus on relapse prevention, but also assess antidepressants’ long-term effects on social functioning and quality of life. Thus far, reliable long-term data on these outcome domains are lacking.

“… 61 This has been explained variously in the literature to be a combination of long-term individual pharmacodynamic adaptations to the presence of the drug, 62 leading to neuropharmacological adaptations that include changes in postsynaptic receptor and auto receptor sensitivity, neurotransmitter synthesis and release, and various downstream molecular and genetic mechanisms in multiple brain systems. 22 , 25 , 63 , 64 These neurobiological adaptations then lead to physical and sensory phenomenon that become manifest when treatment is abruptly removed, being less severe for treatments with longer half-lives. 63 This is shown to resolve if the treatment is briefly reinstituted, even at much lower doses than were previously therapeutic.…”

Section: Current Evidence On How To Discontinuementioning

confidence: 99%

“… 22 , 25 , 63 , 64 These neurobiological adaptations then lead to physical and sensory phenomenon that become manifest when treatment is abruptly removed, being less severe for treatments with longer half-lives. 63 This is shown to resolve if the treatment is briefly reinstituted, even at much lower doses than were previously therapeutic. 63 This has led to the widely accepted recommendation of slow withdrawal to allow for neurobehavioral readaptation to the psychotropic drug.…”

Section: Current Evidence On How To Discontinuementioning

confidence: 99%

Hamlet’s augury: how to manage discontinuation of mood stabilizers in bipolar disorder

Qureshi

Young

2021

Research has generated good quality evidence about the treatment and management of bipolar disorder in acute and, to some degree, sub-acute/continuation phases. This has informed various guidelines about the treatment and management of bipolar disorder (BD). However, for the long-term or maintenance phase of illness, most guidelines peter out and, in the absence of sufficiently high-quality research evidence, remain vague. This is particularly evident for the important clinical question of discontinuing mood stabilizing pharmacological agents after a period of remission has been achieved. The aim of this review is to put together current existing evidence about discontinuing mood stabilizers after a period of remission in order to come up with a structured and coherent strategy for managing such discontinuation and to make recommendations for future research. To this end, we reviewed the main relevant treatment guidelines and subsequent evidence following the publication of these guidelines. The current recommended long-term treatment of BD is usually considered within the same principles applicable to any chronic health condition (e.g. hypertension or diabetes) where the focus is on continuing treatment at minimum effective medication dose often life-long, switching to alternative choice of medication due to side-effects and very few, if any, indications for complete cessation. However, in the absence of strong evidence on long-term treatment and the high rate of non-concordance in BD, medication discontinuation is a very important aspect of the treatment that should be given due consideration at every aspect of the treatment.