As a young elf, I studied ‘medicinal chemistry’; in these courses I learnt about the physiological responses and withdrawal effects produced by many toxic compounds such as alcohol.
As a slightly older elf, at medical school, I learnt about the dangerous reality and possible life-threatening emergencies that accompanied these withdrawal effects.
Then, during psychopharmacology lectures, I learnt about ‘discontinuation effects’ that could result from an abrupt alteration in dose of drugs such as antidepressants. The difference between ‘withdrawal’ and ‘discontinuation’ appeared to be that one was induced by me, as a doctor, whereas the other was owing to addiction.
As an older elf and practicing doctor, I witnessed people ‘discontinuing’ from medications. For example, patients experienced the feeling of electric shocks passing through their bodies after missing two doses of Paroxetine. Again, I wondered about the distinction between ‘discontinuation’ and ‘withdrawal’.
So, it was with some interest that I glanced through a recent table of contents for Psychotherapy and Psychosomatics and saw an Editorial and special article discussing the phenomenon of withdrawal effects and selective serotonin re-uptake inhibitors (SSRI) antidepressants.
Aims
The systematic review by Fava and colleagues aimed to review available literature relating to the phenomenon of SSRI withdrawal effects. The editorial by Chouinard comments on the findings and proposes a classification system for SSRI withdrawal syndromes.
Methods
Fava and Gatti conducted a systematic search of the literature; seeking to identify any paper that referred to SSRI antidepressants and withdrawal or discontinuation effects in its title, abstract or keywords. They included papers that gave examples of at least one discontinuation effect and included a variety of methodologies, e.g. randomised control trials (RCTs), case control studies and single case reports.
Results
- The authors identified 61 studies meeting their inclusion criteria:
- 15 RCTs
- 4 open trials
- 4 retrospective investigations
- 38 clinical case reports
- All SSRI antidepressants were identified as being associated with withdrawal effects
- Such effects occurred much more frequently with Paroxetine (Seroxat) than with other antidepressants
- Despite its longer time to be cleared from the body, Fluoxetine (Prozac) was still associated with withdrawal effects
- Withdrawal effects could be seen after as little as 2 months treatment
- Withdrawal typically occurred within a few days and resolved within weeks
- Frequency of withdrawal effects could not be accurately estimated, but did not appear to be uncommon
- Gradual dose tapering did not eliminate the risk of withdrawal symptoms
- A wide range of physical and psychological effects were apparent (see Table 1 below)
- Variations of this pattern were apparent with delayed onset or prolonged effects described with paroxetine withdrawal effects still being described after one year of follow up
| System involved | Symptoms |
| General | Flu-like symptoms, fatigue, weakness, tiredness, headache, tachycardia, dyspnea |
| Balance | Gait instability, ataxia, dizziness, light-headedness, vertigo |
| Sensory | Paresthesias, electric-shock sensations, myalgias, neuralgias, tinnitus, altered taste, pruritus |
| Visual | Visual changes, blurred vision |
| Neuromotor | Tremor, myoclonus, ataxia, muscle rigidity, jerkiness, muscle aches, facial numbness |
| Vasomotor | Sweating, flushing, chills |
| Sleep | Insomnia, vivid dreams, nightmares, hypersomnia, lethargy |
| Gastrointestinal | Nausea, vomiting, diarrhea, anorexia, abdominal pain |
| Affective | Anxiety, agitation, tension, panic, depression, intensification of suicidal ideation, irritability, impulsiveness, aggression, anger, bouts of crying, mood swings, derealization and depersonalization |
| Psychotic | Visual and auditory hallucinations |
| Cognitive | Confusion, decreased concentration, amnesia |
| Sexual | Genital hypersensitivity, premature ejaculation |
Conclusions
Fava and colleagues conclude:
Clinicians need to add SSRI to the list of drugs potentially inducing withdrawal symptoms upon discontinuation, together with benzodiazepines, barbiturates, and other psychotropic drugs. The term ‘discontinuation syndrome’ that is currently used minimizes the potential vulnerabilities induced by SSRI and should be replaced by ‘withdrawal syndrome’.
Discussion
Both articles use the term ‘withdrawal’ over ‘discontinuation’ advisedly. Fava and colleagues argue that the increasing recent adoption of the term discontinuation is an artefact, at least partially owing to the interest of the pharmaceutical industry, and an emphasis on suggesting that antidepressants do not induce addiction or dependence. The idea of discontinuation symptoms can also be seen as underplaying the severity of these events.
Yet it can be argued that many of the clinical and physiological manifestations of antidepressant action are not dissimilar to those seen in addictive substances such as alcohol (Fava and Offidani 2011). Addiction is associated with a sense of social stigmatisation, however, and it is uncomfortable to discuss in the context of clinical practice.
Chouinard and Chouinard propose diagnostic criteria to classify antidepressant withdrawal according to the nature of the effects observed, including:
- New symptoms (immediate physiological withdrawal symptoms),
- Rebound symptoms, and
- Persistent post-withdrawal syndromes.
They propose that such classification considers only phenomena emerging after 6 months of continuous treatment, although it is noteworthy that the review by Fava and colleagues identified withdrawal symptoms after only 2 months of treatment. Both sets of authors comment on the importance of careful distinction between withdrawal effects and the mis-diagnosis of relapse phenomena.
In their commentary, the Chouinards describe a series of case reports wherein the withdrawal effects are minimised through the use of long acting antidepressants such as Fluoxetine, or co-prescribing of benzodiazepines such as Clonazepam together with the use of psychotherapies such as CBT. They also recommend that, unless there is a direct clinical indication, Paroxetine be avoided entirely.
Fava and colleagues, however, comment on the lack of evidence at present for such approaches and caution against the use of new prescriptions that may prolong withdrawal and cessation efforts.
Discussing the idea of withdrawal effects in antidepressants is complex and uncomfortable. However, the described review clearly demonstrates the existence of the phenomena, and also the lack of research addressing this issue directly. Given the frequency with which these drugs are prescribed and discontinued, this is particularly disturbing.
I am particularly concerned by the lack of evidence to suggest that my own practice of gradual discontinuation over a period of weeks to months is no guarantee against preventing these effects. More research is desperately needed in order that we can adequately grapple with this issue.
Links
Primary study
Fava, G. A., Gatti, A., Belaise, C., Guidi, J., & Offidani, E. (2015). Withdrawal Symptoms after Selective Serotonin Reuptake Inhibitor Discontinuation: A Systematic Review. Psychotherapy and Psychosomatics, 84(2), 72–81. doi:10.1159/000370338 [P&P link]
Other references
Chouinard, G., & Chouinard, V.-A. (2015). New Classification of Selective Serotonin Reuptake Inhibitor Withdrawal. Psychotherapy and Psychosomatics, 84(2), 63–71. doi:10.1159/000371865 [P&P link]
Fava, G. A., & Offidani, E. (2011). The mechanisms of tolerance in antidepressant action. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 35(7), 1593–1602. doi:10.1016/j.pnpbp.2010.07.026 [PubMed Link]
Antidepressant withdrawal: slower and lower tapering of SSRIs
7 years agoMichele B
7 years agoGary Thompson
10 years agoIain Farquhar
10 years agoMichal Osier
10 years agoAnthony
10 years agoCBT for depression in people with learning disabilities
10 years agoAntidepressants for depression: new BAP guidance
10 years agoDebra Sobott
11 years agoTim Bingen
11 years agoMore Discussion of Antidepressant Withdrawal Effects - Mad In America
11 years agoFreigeist
11 years agolorettelavine
11 years agosalimahitchcock
11 years agosandycann2
11 years agoSameiHuda
11 years agosandycann2
11 years agoSameiHuda
11 years agophilosofacespin
11 years agoSameiHuda
11 years agoSameiHuda
11 years agoDrShirleyLock
11 years agoMental_Elf
11 years agoshrinking81
11 years agoTomKearney8
11 years agoMeandmymhmatter
11 years agowhythedarkness
11 years agojonart_therapy
11 years agothinkdrinkdrugs
11 years agoCounsellingMum
11 years agoMental_Elf
11 years agoKRTraumaSupport
11 years agoWerksColorado
11 years agoNewBridgeSvs
11 years agoPrivilegeHealth
11 years agoFadiAbouRihan
11 years agoHWOldham
11 years agoViccimn
11 years agoHealthwatchTame
11 years agoCounsellorPhil
11 years agocaputpurgijs
11 years agokokoromedical
11 years agoshrinking81
11 years agocaputpurgijs
11 years agoshrinking81
11 years agocaputpurgijs
11 years agoDadeMedical
11 years agoMyUSMF
11 years agoPeterFieldHypno
11 years agoshrinking81
11 years agoantonioolives
11 years agoFageMD
11 years agoSuanta1
11 years agoBroadbentAmy
11 years agoRhi
11 years agosuz8863
11 years agoMental_Elf
11 years agoAnselmChuck
11 years agoAnselmChuck
11 years agoKirsikka Kaipainen
11 years agoGagblaKujo
11 years agoBeyondMeds
11 years agoproject499
11 years agoagteien
11 years agoJacobsonDee
11 years agoBeyondMeds
11 years agoBeyondMeds
11 years agosilvergirlsail
11 years agoSiRusson
11 years agoGrandmaAllan
11 years agoMerynEdwards
11 years agojsnyder555
11 years agorecontroller
11 years agothepsychclinic
11 years agoSigNorway
11 years agoAltostrata
11 years agoCharlie Cowtan
11 years agoLouise Hanna
11 years agoScott Inglis
11 years agoJonRottenberg
11 years agodtmaust
11 years agocarlgavin
11 years agoTosaka4398
11 years ago121Therapy
11 years agoGemima_99
11 years agoWellbeing_Works
11 years agoEpi_Life
11 years agoNicolepISIS
11 years agopsysocatsheldon
11 years agoagulbranson
11 years agoolanzapinenight
11 years agoStellaWYChan
11 years agoStegoPax
11 years agogingerdisco99
11 years agoPenny Collins
11 years agoSchizophrenia - Mom's Journey
11 years agoDrFulli
11 years agoDrFulli
11 years agoDrFulli
11 years agoDrFulli
11 years agoKarenFixers
11 years agoKarenFixers
11 years agoHolodeck25
11 years agoSUREteamCardiff
11 years agoMental_Elf
11 years agowongdiagnosis
11 years agolypftlib
11 years agoBrentWRoberts
11 years agoBuffDavis
11 years agoDrAlisonHill
11 years agoMental_Elf
11 years agoKristie Elwell
11 years agoDrLauraNichols
11 years agobarrymcrory1
11 years agoAndrew Brown
11 years agoHHLibService
11 years agoLawnBoy77777
11 years agodrkencarter
11 years agokarmicgirl
11 years agoPrivate_Therapy
11 years agoTrainInnovate
11 years agoNHFTNHSLibrary
11 years agoThe Mental Elf
11 years agoLaura Middlebrook
11 years agoBridget Eley
11 years agoCMH_com
11 years agoabbasian
11 years agohonestpariah
11 years agoB_McT
11 years agoRealDavidCarter
11 years agoGareth Pashley
11 years agoLesley Harrison
11 years agoAlison Parker
11 years agoRecoverySheff
11 years agotgd1982
11 years agoJayarava
11 years agoStoryingShef
11 years agoOcccams
11 years agoJayarava
11 years agoshrinking81
11 years agobernie_hughes
11 years agoSarah McKinlay
11 years agoangela_sheard
11 years agocaputpurgijs
11 years agocaputpurgijs
11 years agoPDinodiya
11 years agoagulbranson
11 years agoLisa Eden
11 years agoHelge Ha
11 years agoiVivekMisra
11 years agoIain_caldwell
11 years agoDrSpriggy
11 years agoGeorgiaBelam
11 years agoJulk
11 years agoOldsoldier8585
11 years agoccooper1309
11 years ago