Persistent adverse neurological effects following SSRI discontinuation (PANES).

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DesigningOne wrote:Persistent adverse neurological effects following SSRI

discontinuation (PANES).

http://www.priory.com/psych/panes.htm

 

Dr Ben Green, MRCPsych,

Consultant Psychiatrist, Halton Hospital, UK and Senior Lecturer, University of

Liverpool, UK

 

Contact the Author at: ben

 

 

 

These prolonged reactions were first described here in Spring 2000. No other

reports are known of, although this condition may well be more widespread than

is presently recognised.

 

Selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome has been

described in the literature as a cluster of symptoms and signs that occur after

SSRIs such as paroxetine, sertraline and fluoxetine have been discontinued

Abrupt withdrawal of antidepressant therapy for 5-8 days is associated with

symptoms such as dizziness, ataxia, paraesthesiae, gastrointestinal and flu-like

symptoms, and other sensory and sleep disturbances. Psychiatric symptoms include

anxiety, agitation, lability of mood, hypersexuality, crying spells, and

irritability.

 

The SSRI discontinuation syndrome appears to be most marked with paroxetine and

to a lesser degree sertraline, with few symptoms seen with fluoxetine (Rosenbaum

et al, 1998). The frequency and severity of these symptoms appear to vary

according to the half-life of the SSRI (Schatzberg et al, 1997). Schatzberg et

al comment that most discontinuation symptoms rare 'short-lived', but that some

effects may be longer lasting.

 

Traditional explanations the pharmacology of SSRIs discuss the effects on the

postsynaptic serotonin receptor, but the SSRIs work at a variety of locations

and their effects reverberate through the nervous and endocrine systems, so that

in animal models there may be altered neuroendocrine function for weeks after

ceasing fluoxetine. Even 60 days after discontinuation of fluoxetine, the

oxytocin response in animals was still significantly reduced by 26% compared

with controls.

 

This report considers four patients on SSRIs who all suffered prolonged

neurological symptoms for months after discontinuing their medication.

 

Mrs A. a 29 year old married lady with a moderate depressive disorder was

switched to paroxetine by her general practitioner after an initial prescription

of dothiepin. She had found the tricyclic dothiepin too sedating and after a

week or so of this medication requested a change. After two weeks on paroxetine

20 mg daily she was reviewed by a consultant psychiatrist who increased the dose

to 40 mg daily. The patient suffered a dystonic reaction to the paroxetine that

required physician review and admission, but apparently responded well to

procyclidine. The paroxetine was discontinued. Unfortunately the dystonic

reaction persisted off all medication and required further medical admission and

the re-prescription of procyclidine. The depression continued unabated and a

tricyclic was started with some improvement in mood. Seven months after the

paroxetine had been stopped the tardive dystonia was noted to be present and to

vary with anxiety levels, body posture, alertness, and emotional state.

 

 

A 35-year-old man (Mr B) was prescribed paroxetine 30 mg daily for depression.

The depression resolved and the paroxetine was continued at the same dose for

two years. The medication was discontinued in a staged way, with reductions to

20, then 10 mg, managed over six weeks or so. Symptoms of withdrawal occurred

throughout this period and comprised vivid nightmares, lability of mood,

irritability, hypersexuality, episodic lightheadedness, episodic electric-shock

like sensations, glove paraesthesiae, and ataxia. These symptoms ended two weeks

after the withdrawal regime was finished. Nevertheless the patient continued to

describe problems of an episodic nature well after the paroxetine had been

discontinued. These episodes lasting hours to days at a time and comprised

paraesthesiae, dizziness, mild ataxia, and slurred speech. These episodes have

occurred intermittently throughout twelve months of follow-up during which time

the patient has been drug-free. There are no focal neurological signs or any

features suggestive of progressive neurological disease, nor was there a family

history of neurological disease.

 

Mrs C., a 29-year-old mother of one, became ill with depression when her son was

aged eight months. She was suicidal and required hospital admission where she

was started on fluoxetine 20 mg daily. The antidepressant worked well and her

mood was restored within four weeks of admission. She was discharged home, but

commented that her sleep was occasionally disturbed by bad dreams and she was

aware of twitching in the bed. She was kept on the fluoxetine for a further

twelve months and at outpatient reviews mentioned that her sleep was still

occasionally disturbed by nocturnal twitching. She said that her husband had

started to sleep separately, because he was 'tired of being kicked' in the

middle of the night. The fluoxetine was discontinued eighteen months after the

admission. Mrs C described no worsening of her mood and was euthymic and

outpatient review. However, she was distressed to report that her nocturnal

twitching, which took the form of sudden myoclonic jerks of her limbs, had

actually worsened off fluoxetine. During the day these abnormal involuntary

movements were less marked and more easily disguised, but nonetheless

problematic for the patient. At follow-up eight months after discontinuation the

untoward myoclonic jerks were continuing. There are no focal neurological signs

or any features suggestive of progressive neurological disease, nor was there a

family history of neurological disease.

 

 

 

Mrs D., a 49 year old health professional was prescribed 20 mg paroxetine daily

in April 2000 for a depressive disorder. This relieved the depression, but after

three months the patient started to develop paresthesiae in the right hand, and

some weeks later experienced her fingers being 'fumbly'. She visited her GP and

complained that although her mood was satisfactory there were unpleasant side

effects. He asked her to reduce the dose to 10 mg daily. Mrs D began to

experience painful, restless legs at night and vivid dreams. The tingling in her

hand spread into her body and head. After a week of the 10 mg dose the patient

discontinued the paroxetine altogether in the belief that the paroxetine would

be out of her system in a few days and her symptoms would subside. The symptoms

however persisted. She took a week off work, but the following symptoms

persisted for the next three months:

 

* paraesthesiae in hands and feet spreading up arms and legs intermittently

* stiffness in calf muscles

* unsteadiness on her feet with wide gait

* clumsy fingers

* loose bowels

* disinhibited mood

 

 

These symptoms appeared worst at the end of the day, following heavy physical

work, and with even small amounts of alcohol. By December, four months after

discontinuing the paroxetine most of the symptoms had reduced in severity to

near normal.

 

Mrs E., a 48 year old woman was prescribed citalopram by her GP for eleven

months. The indication for the prescription was chronic anxiety. For fifteen

months following the discontinuation of this therapy she suffered headaches and

dizziness. She also complained of a fluttering sensation across her scalp. To

date there has been little improvement.

 

 

Discussion

 

These five patients all demonstrated neurological side effects or withdrawal

effects that occurred either during SSRI therapy or in the discontinuation phase

associated with an SSRI. However, these neurological effects persisted for

months after discontinuation and in most cases persist up until the time of

writing. Whether the association with treatment or discontinuation is causal

could be debated, but the chronological association seems good and three of the

five patients (Mr. B, Mrs C and Mrs D) were psychotropic drug-naïve at the start

of the SSRI therapy and wholly drug free following this.

 

The three SSRIs prescribed and mentioned above (fluoxetine, paroxetine and

citalopram) differ in terms of structural and pharmacokinetic properties, but

share a relatively selective ability to affect serotonin re-uptake. Paroxetine

and citalopram have a relatively short half-life and it may be that they are

more prone to association with the discontinuation effects and PANES.

 

It may be that this common ability of the SSRIs (to affect serotonin re-uptake),

or an indirect consequence of this ability is responsible for these persistent

adverse neurological effects. These effects appear to have been first described

in this report.

 

There is something of a similarity to the effects seen after benzodiazepine

discontinuation (Ashton, 1987). In benzodiazepine withdrawal the symptoms occur

1-2 weeks after withdrawal and may persist to some degree. Th mechanism is

thought to be related to GABA-ergic systems.

 

Further case reports and surveillance data are needed to establish the

significance or otherwise of what we propose to be persistent adverse

neurological effects of SSRIs (PANES).

 

 

References

 

Ashton, H (1987)Brain systems, disorders and psychotropic drugs. Oxford, OUP.

 

Raap DK; Garcia F; Muma Na et al. (1999) Sustained desensitization of

hypothalamic 5-Hydroxytryptamine1A receptors after discontinuation of

fluoxetine: inhibited neuroendocrine responses to

8-hydroxy-2-(Dipropylamino)Tetralin in the absence of changes in Gi/o/z

proteins. J Pharmacol Exp Ther, Feb, 288:2, 561-7.

 

Rosenbaum JF; Fava M; Hoog SL; Ascroft RC; Krebs WB (1998) Selective serotonin

reuptake inhibitor discontinuation syndrome: a randomized clinical trial [see

comments] Biol Psychiatry, 1998 Jul, 44:2, 77-87.

 

Schatzberg AF; Haddad P; Kaplan EM et al. (1997) Serotonin reuptake inhibitor

discontinuation syndrome: a hypothetical definition. Discontinuation Consensus

panel. J Clin Psychiatry, 1997, 58 Suppl 7:, 5-10

 

 

Version 1.0 published Spring 2000

Version 2.0 published November 2000

Version 2.0 published December 2000

 

 

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