THERE is “probably no good evidence” for long-term use of antidepressants but very little research into how patients can discontinue treatment safely, according to one of the academics behind a major new review into the drugs.

Dr Mark Horowitz, a research fellow and psychiatrist-in-training at University College London who has studied the neurobiology of antidepressants said studies have consistently failed to distinguish between disease relapse and withdrawal symptoms, adding that it was “absolutely incredible” that millions of people are being left on the drugs for years.

HeraldScotland: (Source: Scottish Government)(Source: Scottish Government)

In Scotland, more than one in five people (21.6 per cent) are being prescribed antidepressants and half have been taking them for more than three years.

As of 2019/20, 960,000 people in Scotland were taking antidepressants.

The figure has increased steadily over the past decade, from 665,000 in 2010/11.

As antidepressants are also sometimes prescribed for non-mental health conditions - such chronic pain or bedwetting in children - the figures provide a gauge, but not an exact count, for diagnoses of depression, anxiety, post-traumatic stress, and obsessive compulsive disorders within the population.

READ MORE: Campaigners urge MSPs to tackle 'health scandal' of prescription pill harm

However, concerns about the lack of evidence to support increasing rates of long-term use have been highlighted in a new Cochrane Review carried out by Dr Horowitz and Belgium-based researcher and GP, Dr Ellen Van Leeuwen.

Cochrane Reviews are considered the gold-standard for evaluating the reliability of evidence behind medical treatments, and are used as a guide by doctors and healthcare providers worldwide.

Drs Horowitz and Van Leeuwen identified more than 1000 studies on starting antidepressants but just 33 randomised control trials that examined stopping them.

“It’s clear that this area needs urgent attention,” said Dr Van Leeuwen.

She added: “As a GP myself, I see first-hand the struggles many patients have coming off antidepressants.

“It’s of critical concern that we don’t know enough about how to reduce inappropriate long-term use or what the safest and most effective approaches are to help people do this.”

HeraldScotland: Slide produced for Cochrane Review highlighting distinctions and similarities between relapse and withdrawal symptomsSlide produced for Cochrane Review highlighting distinctions and similarities between relapse and withdrawal symptoms

The issue of prescribed drug dependence and withdrawal has gained increasing attention in recent years, including through a petition brought to the Scottish Parliament in 2017 seeking help for patients harmed as a result.

It closed last month, having attracted hundreds of written submissions in support from medical professionals, charities, and patients, some of whom described harrowing experiences of being driven to suicide attempts as they tried to wean themselves off prescribed medication including antidepressants or benzodiazepines.

HeraldScotland: The Cochrane Review found 'very low' certainty of evidence about how and when can safely discontinue antidepressantsThe Cochrane Review found 'very low' certainty of evidence about how and when can safely discontinue antidepressants

Although some patients can come off the drugs slowly and successfully, others experience debilitating effects such as panic, dread, insomnia, agitation or ‘brain zaps’ - sensations like electric shocks in the head and limbs.

One respondent to the petition told how withdrawal from antidepressants left her with “terrible panic and inner turmoil on a scale I had never encountered before”, eventually leading her to try to end her life.

Dr Horowitz has experienced the problem first-hand.

He has been tapering himself off antidepressants now for more than two years, after taking them for 18 years from the age of 21.

“It’s been a very difficult process,” he told the Herald on Sunday.

“As a patient, I’m very unhappy that I was not told when I started them that they would be hard to stop.”

READ MORE: Number of patients harmed by prescription drug withdrawal 'too difficult to say'

Despite reducing the dose incrementally he has still experienced panic attacks, insomnia, and “great trouble” concentrating.

“I didn’t have any of those things before starting antidepressants. I never had trouble sleeping, never had panic attacks - I was just a mildly unhappy young man.”

Crucially, the Cochrane Review says future studies must monitor patients over a longer period (most of the tapering regimes studied lasted four weeks or less, in contrast to new guidelines from the Royal College of Psychiatrists which advise taking months or years to stop antidepressants).

In addition, all failed to disentangle relapse from withdrawal - a problem which has led to many real-world patients either being put back on antidepressants, sometimes at higher doses, or being diagnosed with new disorders leading to further pharmaceutical intervention.

HeraldScotland: Number of adults in Scotland receiving at least one prescription by medicine class for financial years 2010/11 to 2019/20 (Source: Scottish Government)Number of adults in Scotland receiving at least one prescription by medicine class for financial years 2010/11 to 2019/20 (Source: Scottish Government)

Dr Horowitz said the only way to avoid that “was to take the people off very slowly”, over months and years, so that genuine relapses could be correctly identified.

However, he added that existing guidance used by clinicians is in itself based on flawed research.

“They don’t compare people who are off the drugs to people who are on the drugs for two years," he said. 

“They take people who are already on the drugs and they get half of them to stop and half to continue and then check people for relapse.

"And they find that they relapse more when they come off the drug.

“But they take the people off the drug over a few days, and they don’t measure withdrawal symptoms, so actually the NICE guidance saying we should be treating people for six to 12 months or two years, is flawed.

“That’s one of the things this review is pointing towards. It’s probable that there is no good evidence for long-term treatment.”

HeraldScotland: Duration of time on medication since last three-month break, by total number of adult patients per prescribed drug, as of March 2018 (Source: Scottish Government)Duration of time on medication since last three-month break, by total number of adult patients per prescribed drug, as of March 2018 (Source: Scottish Government)

For too long, he added, there has been a culture of denial about the problem which has been unhelpful for patients.

"Psychiatry has to stop being so defensive and crying out 'pill shaming' to shutdown what are genuine concerns about patients' welfare," said Dr Horowitz.

There is no data yet clarifying whether the number of people on antidepressants in Scotland has increased during the pandemic.

HeraldScotland: The percentage of adults taking antidepressants and/or other key prescription drugs associated with dependence is higher in Scotland than England in all five categories, and for both sexes The percentage of adults taking antidepressants and/or other key prescription drugs associated with dependence is higher in Scotland than England in all five categories, and for both sexes

Figures for England show that while antidepressant prescriptions were higher at the end of 2020 than 2019, the rate of increase had actually slowed compared to previous years.

The review has been welcomed by Marion Brown, a psychotherapist from Helensburgh who brought the prescription dependence petition to the Scottish Parliament after becoming concerned about the number of traumatic withdrawal experiences among her clients.

HeraldScotland: Marion Brown, who has been campaigning for recognition and help for patients harmed by withdrawal from antidepressantsMarion Brown, who has been campaigning for recognition and help for patients harmed by withdrawal from antidepressants

She also believes that antidepressant withdrawal contributed to her late husband Charles's suicide in November 2011.

The 58-year-old GP had Addison’s disease - a rare hormonal disorder which also causes depression - and had been taking the antidepressant Seroxat at a low dose for 25 years.

When he retired he tried to gradually stop the medication.

“It’s only now, looking back, that I recognise what was going on with him,” said Mrs Brown. “It wasn’t something anybody talked about.

“He had terrible agitation. He couldn’t sit still. Gut problems. Terrible insomnia - he didn’t sleep for over two weeks. He kept saying ‘I want to kill myself’.

“He just felt terribly ill, physically, yet all his vital signs came out okay.

“As a doctor he’d been part of the Defeat Depression campaign in the 1990s - he’d been incentivised to prescribe these drugs. He believed the hype.

"And we’re still living with the legacy of that because there’s so many people who’ve never been able to come off the drug.”

READ MORE: U-turn as Royal College says should be warned about antidepressant withdrawal risk

On March 12, the Scottish Government’s Short Life Working Group (SLWG) on prescription medicine launched a consultation on its draft recommendations, including the creation of an out-of-hours helpline for patients suffering from dependence and withdrawal symptoms and “further research on the prevention and treatment of dependence on, and withdrawal from, prescribed medicines".

As well as antidepressants, it covers tranquilisers such as benzodiazepines and Z-drugs, opioid painkillers, and gabapentinoids prescribed for anxiety and nerve pain.

A spokeswoman for the Royal College of Psychiatrists in Scotland, said: “For people with depression, antidepressants can be a lifeline.

"Some people experience withdrawal symptoms when trying to come off them, and reducing the dose slowly before stopping, can help.

“The more we understand about side effects, withdrawal symptoms, and how to reduce them, the more people we will be able to help.

"That’s why it’s vital to keep engaging patients, researchers and mental health professionals in an open conversation about the benefits and potential harms of antidepressants.”

The College's online guide, ‘Stopping Antidepressants’, can be accessed for free here