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Antidepressants not ‘dependence-forming’ but cause withdrawal, determines NICE guideline


NICE: Antidepressants not ‘dependence-forming’ but can cause withdrawals


Antidepressants are not ‘dependence-forming’ drugs, although they can cause withdrawal symptoms, a final NICE guideline has concluded.

The guideline covers adult safe prescribing and withdrawal management for medicines such as opioids, benzodiazepines, gabapentinoids, Z‑drugs and antidepressants.

A draft version of the guidelines published in October referred to these as ‘medicines associated with dependence or withdrawal symptoms’.

But the new NICE guideline, published yesterday, referred to the same set of drugs as ‘a dependence-forming medicine or antidepressant’.

It said: ‘Medicines associated with dependence include benzodiazepines, Z‑drugs (such as zopiclone and zolpidem), opioids, gabapentin and pregabalin. 

‘Antidepressants, although historically not classified as dependence-forming medicines, can nevertheless cause withdrawal symptoms when they are stopped.’

The new guideline published today also rubberstamped the draft’s recommendations that GPs should provide regular reviews for patients on antidepressants and drugs for chronic pain that may cause dependency or withdrawal.

And it confirmed that secondary care clinicians who ‘recommend a dependence-forming medicine or antidepressant to be started or continued in primary care’ should explain to the patient that their primary care team will prescribe and review this.

However, it added: ‘If the primary care team declines to prescribe the medicine, or wishes to delay it, the secondary and primary care teams will discuss the medicine and involve the person in these discussions, explaining the reasons for any delay.’

The guideline also reiterated that GPs deciding about prescribing ‘dependence-forming’ medicines or antidepressants should determine whether there are any factors that could increase a patient’s risk of developing problems associated with dependency.

However, it added that GPs should ‘not withhold the medicine solely on the basis of one of these factors’. 

And it said that the prescription could be delayed if GPs need ‘additional time’ to ‘consider options and consult with colleagues’.

The NICE guideline said: ‘Acknowledge that these decisions are also difficult for the prescriber particularly when supporting a person who is distressed, and in the presence of risk factors for developing problems associated with dependence, and that additional time may be required to consider options and consult with colleagues.

‘Consider delaying prescribing if the person needs more time to think about their options or the prescriber needs to consult with other members of the healthcare team. If prescribing is delayed, ensure that a follow-up appointment is arranged.’

It also recommended that GPs ‘take steps to reduce the risk of developing problems associated with dependence, for example starting at a low dose, and consider avoiding modified-release opioids’.

‘Once an effective dose has been established, avoid automatically increasing the dose if the response is not sustained’, it added.

And it recommended a tailored approach to agreeing any dose reduction schedule with patients, including ensuring the planned rate of reduction is ‘acceptable’ to them.

It said GPs should consider giving patients ‘additional control’ over the pace of reduction, for example by ‘issuing their usual daily dose in a form that allows them to reduce the amount in small decrements at a pace of their choosing, rather than issuing successive prescriptions for reduced daily doses’.

It added: ‘Explain that although withdrawal symptoms are to be expected, the reduction schedule can be modified to allow intolerable withdrawal symptoms to improve before making the next reduction.’

The new guidance does not cover the prescription of gabapentinoids for epilepsy, opioids for acute pain, cancer pain or at the end of life, or management of illicit drug dependence.

It follows new draft guidance on stopping antidepressants – published in November – that said GPs could be supporting patients for months if they experience severe side effects which could include suicidal thoughts and panic attacks.

This was NICE’s third attempt at drafting a guideline on that topic, with expected final publication next month.

NICE had previously revised its depression guidelines in 2019 to warn of ‘severe’ and lengthy antidepressant withdrawal symptoms, having originally said such symptoms were ‘mild’. 

It follows a 2019 report from Public Health England that warned that one in four patients had been given a prescription for a potentially addictive medicine, including antidepressants.

Safe prescribing and withdrawal management for medicines associated with dependence or withdrawal symptoms

Frequency of reviews

Offer regular reviews (by phone, video or face to face) to people taking an opioid, benzodiazepine, gabapentinoid, Z‑drug or antidepressant. Base the frequency of reviews on:

  • the person’s preferences and circumstances

  • the type of medicine they are taking and the dose

  • factors that might indicate a need for frequent reviews, for example if:

    • the person has additional care needs (such as people with a learning disability or cognitive impairment)

    • the person is taking the medicine for the first time

    • there are potential adverse effects or problems associated with dependence

    • the medicine is being used outside its licensed indications

    • there is potential for misuse of the medicine.

Consider increasing the frequency of reviews during dose adjustment. Take into account the person’s clinical and support needs when agreeing review frequency.

Offer extra, unscheduled reviews when needed, for example if the person:

  • reports adverse effects from the medicine

  • becomes pregnant or is planning pregnancy

  • has a change in their physical or mental health condition, or social circumstances

  • starts taking medicines from a different prescriber

  • requests a change in dose.

Working with other healthcare professionals

Healthcare professionals in secondary care who recommend a dependence-forming medicine or antidepressant to be started or continued in primary care should explain to the person that:

  • the medicine will be prescribed by their primary care team

  • the primary care team will need to review the medicine

  • if the primary care team declines to prescribe the medicine, or wishes to delay it, the secondary and primary care teams will discuss the medicine and involve the person in these discussions, explaining the reasons for any delay

  • the secondary care team might not continue to manage and provide the medicine if this is agreed after discussions.

Making decisions about prescribing and taking a dependence-forming medicine or antidepressant

When making decisions about prescribing medicines, determine whether there are any factors that might increase the person’s risk of developing problems associated with dependence, but do not withhold the medicine solely on the basis of one of these factors. Explain and discuss the risk with the person. Factors that might increase risk include:

  • a comorbid mental health diagnosis

  • a history of drug or alcohol misuse

  • not having a clear, defined diagnosis to support the prescription

  • taking an opioid together with a benzodiazepine.

Recognise and acknowledge that decisions about medicines can be difficult for a person who is in distress.

Acknowledge that these decisions are also difficult for the prescriber particularly when supporting a person who is distressed, and in the presence of risk factors for developing problems associated with dependence, and that additional time may be required to consider options and consult with colleagues.

Consider delaying prescribing if the person needs more time to think about their options or the prescriber needs to consult with other members of the healthcare team. If prescribing is delayed, ensure that a follow-up appointment is arranged.

Prescribing strategies

Take steps to reduce the risk of developing problems associated with dependence, for example starting at a low dose, and consider avoiding modified-release opioids. Explain the importance of these steps to the person.

Discuss with the person the range of doses likely to be safe and effective. Start with a low dose and agree frequent, regular reviews to ensure that timely adjustments can be made to test effectiveness, safety and acceptability and to find the lowest effective dose. Once an effective dose has been established, avoid automatically increasing the dose if the response is not sustained.

Dose reduction

When agreeing a dose reduction schedule with the person:

  • explain the risk of abrupt discontinuation and that the rate of safe withdrawal varies between people and can vary over time for the same person

  • balance the risk of adverse events from continued exposure to the medicine with minimising the risk of withdrawal symptoms by slow dose reduction and withdrawal

  • ensure that the planned rate of reduction is acceptable to the person

  • explain that although withdrawal symptoms are to be expected, the reduction schedule can be modified to allow intolerable withdrawal symptoms to improve before making the next reduction

  • consider giving the person additional control over the process of dose reduction (for example, by issuing their usual daily dose in a form that allows them to reduce the amount in small decrements at a pace of their choosing, rather than issuing successive prescriptions for reduced daily doses)

  • agree regular intervals for reviewing and adjusting the reduction schedule as needed

  • ensure the person knows who to contact if problems occur.

Source: NICE

READERS' COMMENTS [4]

Patrufini Duffy 20 April, 2022 6:10 pm

Yet more bullet points. Pulse should next investigate, who is actually profiteering from mental health and it’s empty contracts? Into whose pockets is “all” this money vanishing, at the demise of the common person, who is being set up to fail in misery, hopelessness and mediocrity, in a somewhat orchestrated plan.

Timothy Roger Moss 21 April, 2022 3:25 pm

“Antidepressants are not dependence-forming drugs, although they can cause withdrawal syndromes”.
The alleviation of intense AD withdrawal syndromes by returning to the previous (higher dose) or re-introducing the withdrawn SSRI/SNRI/Atypical antidepressant, might reasonably be considered to be evidence of neuro-physiological dependence? Misdiagnosis of A.D. withdrawal syndromes as ‘recurrence’ has the potential to devalue the published evidence base.
Intense withdrawal syndromes, including AKATHISIA, and suicidal ideation have been reported in healthy volunteer studies from the 1980’s:
‘It was clear that volunteers exposed to these drugs could have withdrawal symptoms after only two weeks on treatment. The symptoms included anxiety, depression, sexual dysfunction, suicidality, dizziness, gut and other problems. These drugs were sold as non-dependence producing in contrast to benzodiazepines. There were however more reports of dependence/withdrawal linked to (named SSRI) in three years of (named SSRI) being on the market than from all benzodiazepines combined in the previous 20 years’.
Although the importance of hyperbolic dose-reduction is eluded to, the severity, and extended duration of AD withdrawal syndromes, and the risk of withdrawal induced AKATHISIA surely merits detailed emphasis of the potential benefit of smaller and smaller dose reductions at each stage?
In view of the range of strongly held opinion regarding AD toxicity/withdrawal/efficacy/safety, every care has been taken in referring to the quotation above. The comment is made in good faith.

John Glasspool 22 April, 2022 7:06 am

If some people had their way doctors would prescribe very little indeed: antidepressants- Bad. Anxiolytics- Bad. Gabapentinoids- Bad. Analgesics- Bad. NSAIs- Bad.

Patrufini Duffy 22 April, 2022 3:06 pm

Cocaine and cannabis are dependent forming. And alcohol. But lets not talk about that for now. Taboo subject in the UK.

https://www.spectator.co.uk/article/deaths-of-despair-how-britain-became-europe-s-drugs-capital