Table 1.
Peer-reviewed publications identified through database search.
| Article | Brief overview | Conclusions | |
|---|---|---|---|
| Clinical studies | Randomized controlled trial: Tint et al. [2008] |
28 patients treated with paroxetine, fluoxetine or venlafaxine were randomised to a 3-day (n = 15) or 14-day (n = 13) antidepressant taper schedule. Discontinuation symptoms were assessed using MADRS and DESS questionnaires. | No significant difference reported in symptoms experienced by those undergoing longer or shorter taper schedules. Authors suggests drug half-life more important than taper duration |
| Randomized controlled trial: Montgomery et al. [2004] |
198 patients treated with paroxetine and agomelatine were randomized into four groups. Two groups continued treatment (paroxetine n = 61, agomelatine n = 61) whilst two groups discontinued using placebo (paroxetine n = 43, agomelatine n = 27). Discontinuation symptoms measured using DESS. | Study found no discontinuation syndrome associated with agomelatine and suggest this drug may be useful in the treatment of patients who have experienced adverse symptoms withdrawing from other antidepressant medication. Study demonstrated occurrence of discontinuation syndrome with paroxetine. | |
| Analysis: Baldwin et al. [2007] |
Analysis of randomized controlled studies of escitalopram in major depression and anxiety disorders evaluated by the DESS checklist. This study primarily investigates the differences between discontinuation syndromes and whether duration of treatment impacts upon occurrence. | It was found that duration of treatment was not associated with any increase in the incidence of symptoms occurring. Although the data does not suggest any effect of tapering within the doses used, the authors note that following abrupt withdrawal in the SAD group there were more incidences of some symptoms (e.g. sweating and dizziness) than in the MDD group which used a taper method. | |
| Analysis: Himei and Okamura [2006] |
A retrospective analysis investigating the clinical records of outpatients diagnosed with major depression from two centres in West Japan. All patients had been treated with paroxetine during the previous 5 years and were divided into groups based on the experience of a discontinuation syndrome. Of 385 patients, 41 experienced a discontinuation syndrome. | Study found that those patients who abruptly withdrew treatment or who had experienced adverse effects during early phase of treatment were more likely to experience discontinuation symptoms. The authors recommend tapering gradually and monitoring those patients with prior adverse reactions to medication. | |
| Observational cohort study: van Geffen et al. [2005] | Investigation into number of discontinuation symptoms reported following SSRI withdrawal in patients with a range of diagnoses who tapered dose (n = 48) as compared with those who abruptly discontinued (n = 14) as measured by DESS checklist. | Significantly more adverse effects as a result of discontinuation were reported by those patients who withdrew medication abruptly. Authors recommend tapering to avoid unpleasant symptoms | |
| Case series | Cromarty et al. [2010] | Three cases (AB style design) of combined CBT and antidepressant withdrawal. All patients had previously attempted withdrawal. Daily self-monitoring diaries were used to measure target variables. | Authors state that it can be argued that CBT intervention has a beneficial effect, particularly in reducing patient anxieties about discontinuing medication. |
| Consensus panel recommendations | Schatzberg et al. [2006] | Summary of recommendations for the discontinuation of SSRIs. | Panel recommends gradual dose tapering and potentially switching to longer-acting drugs such as fluoxetine alongside close patient monitoring and education about syndrome. |
| Reviews | Ogle and Akkerman [2013] | Systematic literature review. | Authors note that they identified no single or complete guideline for antidepressant discontinuation. Discusses taper schedules and that there is a lack of agreement on the most effective taper duration (4 weeks or 4 months). |
| Phelps [2011] | Review of recent literature on antidepressant treatment for narcolepsy. | Author argues that 3 months or more are required for tapering based on results from narcolepsy studies which suggest that this is the time it takes for the body to stabilize following drug exposure. | |
| Lader [2007] | Review and discussion on discontinuing treatment. | Recommends tapering but notes that this does not eliminate syndrome although it does appear to lessen it. Author also suggests reinstating drug in severe cases of the syndrome and initiating a slower taper rate. | |
| Zarowitz [2006] | Review and discussion of gradual dose tapering in antidepressants. | Author recommends tapering by no more than 25% every 1–2 weeks. | |
| Reid and Cameron [2009] | Drug review in Prescriber. | Authors cite NICE as recommending slower tapering following restarting of drug in severe cases of discontinuation syndrome and that all patients should be made aware prior to drug withdrawal of potential side effects. | |
| Haddad and Anderson [2007] | Review on recognizing and managing the symptoms of discontinuation syndrome. | Authors recommend tapering although note that the BNF suggest 4 week tapering whilst other authorities advise slower dose reductions and point out the lack of controlled data. Advise reinstating drug and commencing slower taper (using liquid preparations) if extreme symptoms and the possibility of switching to fluoxetine. Authors also emphasise patient education. | |
| McHugh and Krishnadas [2011] | Review on stopping drugs in the Prescriber. | Authors state that 4-week taper is generally recommended but add that towards the end a slower taper may be required and that many drugs are available in liquid form to enable this. Patients should also be informed before and during discontinuation as to possible side effects. | |
| Warner et al. [2006] | Review and discussion of the antidepressant discontinuation syndrome. | Note that closely monitored taper of 6–8 weeks advisable although if doses are low this could possibly be more rapid. Authors indicate that fluoxetine may need no taper. | |
| Muzina [2010] | Review of ‘Tapering tips’ | Recommends slow tapering, reinstating drug and tapering more gradually if severe. Also advises substituting with fluoxetine and provides examples with doses for doing so in the case of venlafaxine discontinuation. | |
| Edwards [2006] | Review on stopping drugs in the Prescriber. | Recommends 4-week withdrawal and reinstating drug then more gradually reducing it in severe cases of the syndrome. Also suggests substitution and treatment of benzodiazepines for those patients with extreme symptoms. | |
| Renoir [2013] | A review of the clinical evidence of the SSRI discontinuation syndrome. | Gradual tapering of the drug is recommended along with adequate patient and caregiver education as to the symptoms of the syndrome. |
BNF, British National Formulary; CBT, cognitive behavioural therapy; DESS, discontinuation-emergent signs and symptoms questionnaire; MADRS, Montgomery–Åsberg Depression Rating Scale; MDD, major depressive disorder; SAD, seasonal affective disorder; SSRI, selective serotonin reuptake inhibitor.