They were once considered a wonder drug for anxiety, stress and insomnia.

As prescriptions for benzodiazepines boomed in the 1960s some of the best known brands, such as Valium and Ativan, became household names immortalised as "mother's little helper" in a song by the Rolling Stones.

By 1979, around 30 million prescriptions for these tranquilisers were being issued in the UK - but the evidence was mounting that they may not be the panacea they first appeared.

As early as 1968 the Journal of the American Medical Association observed that a number of psychiatric patients had become suicidal after only a few days' use, and noted how the condition of others worsened when they came off the treatment.

By 1982, Britain's Medical Research Council (MRC) in Britain was recommending that large-scale studies be undertaken to examine the long-term impact of benzodiazepines after research by a leading psychiatrist showed brain shrinkage in some patients similar to the effects of long-term alcohol abuse.

Critics described the drugs as "worse to withdraw from than heroin" and a "medical disaster akin to Thalidomide".

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

It was against the spectre of abuse and dependence that doctors welcomed the arrival of a new class of antidepressant in the 1980s which were widely considered to be safe and non-addictive - just as 'benzos' had once replaced barbiturates.

Today, selective-serotonin reuptake inhibitors (SSRIs) are the most commonly used form of antidepressants but, as a Panorama documentary this week highlighted, there are signs that history was soon repeating itself.

A confidential Pfizer memo leaked to the programme showed that the drug company, which manufactured the antidepressant Zoloft (sertraline), had been aware that some patients were exhibiting signs of dependence back in 1996.

In a document written ahead of a meeting with Norwegian regulators in 1996, officials for the pharmaceutical giant noted that "we should not volunteer to describe the withdrawal symptoms but have an agreed list prepared in case they insist".

These included "sensory disturbances, sweating, insomnia, nausea, agitation, anxiety".

The Herald: The number of people on antidepressants in Scotland has steadily increased, although they can also be prescribed for conditions such as chronic pain. Many patients are also long-term usersThe number of people on antidepressants in Scotland has steadily increased, although they can also be prescribed for conditions such as chronic pain. Many patients are also long-term users (Image: PHS)

By 1998, Harvard medical school researchers were raising the alarm after their own research found that more than 60% of patients who took sertraline or paroxetine (brand name Seroxat) for between four months to two years would experience withdrawal symptoms after stopping, including severe and lasting harm in a small group of patients.

For some it was easier to stay on the medication permanently than suffer the side effects of trying to stop.

READ MORE: Scots psychiatrist says Royal College 'gaslighted' him in antidepressant row 

Despite these red flags, the message from psychiatry over the next 20 years remained that withdrawal from antidepressants was "mild, self-limiting and tends to resolve over a week".

For many patients that will have been the case, and for many others the benefits of taking them have been nothing short of life-saving.

But it is also true that campaigners who tried to draw attention to a darker side of antidepressants were shouted down, dismissed, or accused of "pill-shaming".

Doctors, psychiatrists and academics - sometimes speaking out only after direct, personal experience of withdrawal - were gaslit as cranks or met with outright hostility. 

All too often questioning the efficacy of antidepressants was conflated with diminishing the seriousness of depression itself as an illness.

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Yet a growing number of patients and medical professionals - including here in Scotland - refused to be silenced.

A petition to the Scottish Parliament in 2017 - backed by the BMA and mental health charities - called (without success) for the creation of dedicated support services for people struggling with dependence on prescription pills, including antidepressants.

Harrowing personal testimonies described everything from a loss of sexual function and constant "brain zaps" to feelings of "profound terror" and suicidality.

Some had been prescribed the drugs for mild social anxiety only to be plunged into psychosis during withdrawal, even if they spent months gradually tapering down the dose.

READ MORE: Scotland's secret 'addicts' - the patients hooked on antidepressants, and harmed by withdrawal

The goalposts only really shifted in 2020 when the UK's Royal College of Psychiatrists finally conceded that withdrawal could be a significant problem for a small minority and issued updated patient guidance setting out more detailed steps on how to stop.

Plenty of questions remain, however, including the ongoing controversy over the "chemical imbalance" theory.

The problem is that no one knows exactly what causes depression or why, for some, SSRIs work.

Nonetheless, the idea that they reverse low levels of serotonin in the brain took hold in the 1980s and half of all the SSRI patient leaflets approved by the UK medicines regulator still promote the message that the drugs "help to correct certain chemical imbalances in the brain that are causing the symptoms of your illness".

This was contested by a review published in the Nature journal Molecular Psychiatry in July 2022, which claimed there was "no consistent evidence" that low levels of serotonin cause depression.

As scientific papers go, it caused something of a sensation; to date it has been downloaded more than one million times.

The Herald: The role of serotonin in depression is still contestedThe role of serotonin in depression is still contested (Image: Getty)

The debate is far from settled, however.

On June 16, a group of 36 experts put their names to a comment in rebuttal - also published in Molecular Psychiatry - which accuses the previous paper of being "methodologically flawed", presenting "no new analysis", and ignoring "basic facts regarding the pharmacology of serotonin receptors".

Professor Alan Young, its co-lead author and head of academic psychiatry at King's College London, insisted that the chemical imbalance theory had only ever been "a simplistic view to explain how brain changes occur in depression in a more accessible way".

He added: "Any criticism of the chemical imbalance theory truly misunderstands why it was developed and used by researchers and clinicians.

"Nevertheless, brain changes do occur in the brain of depressed people, including changes in serotonin, and thus the conclusion that this 2022 umbrella review reaches are incorrect."

For the million or so Scots currently taking antidepressants, however, none of this solves the even knottier question of 'what is the alternative?'.

But if history has taught us anything, it will probably be a new pill.