How did benzodiazepines grow into the most broadly prescribed class of drugs in the world in just a decade?
The Stones’ 1966 hit ‘Mother’s Little Helper’, a cryptic and catchy song to Valium. The words are a social critique on benzodiazepines, which had just hit the market a few years prior and become wildly popular, particularly among American housewives.
What a drag it is getting old
‘Kids are different today,’ I hear ev’ry mother say
Mother needs something today to calm her down
And though she’s not really ill
There’s a little yellow pill
She goes running for the shelter of a mother’s little helper.
– The Rolling Stones
In the late 1800s, drug producers had been seeking for a new, non-addictive anti-anxiety prescription. Before, patients were given opiates – with predictably unfavourable results. Then came barbiturates, which were also addressed as too addictive. After that, doctors began prescribing antipsychotic drugs known as phenothiazines, but those drugs triggered severe side effects such as uncontrollable facial gestures.
The late Leo Sternbach – a research chemist – began botching with an unknown class of mixtures: the BZDs, or benzodiazepines. Over many years, he tested some 40 BZDs, but all proved ineffective. In 1956, after adding methylamine (a colourless gas derived from ammonia) to one compound, he designed a white powder that made mice drowsy and calm. The Food and Drug Administration approved Librium, the first-ever benzodiazepine, in 1960 and Valium in 1963.
Receptor in the Brain
Benzodiazepines lock onto a receptor in the brain, which then initiates a neighbouring neurotransmitter known as GABA. GABA release makes people calm and sleepy. The drugs can trigger that GABA rush in minutes, allowing a user to sense more relaxed almost instantly. Initially, benzodiazepines were praised as a medical miracle, and they soon became the most widely prescribed class of drugs in the world. Even though the drugs’ addictive characteristics have become apparent, they remain broadly available and are often prescribed for longer than the suggested 2–4 weeks.
Tolerance to the drugs is considered to develop because benzodiazepines reduce the response of receptors in the brain. That suggests a benzodiazepine user needs to keep ramping up the drug’s dosage to trigger the same calming influence of GABA. The drugs are also non-specific: they act on multiple subunits of GABA, which administer different actions, such as anxiety, restfulness, motor control and cognition.
Even if a person goes on drugs to relieve social stress, they are invariably modifying how they think, sleep and even move. This illustrates why a person coming off benzodiazepines may experience wholly new symptoms, such as panic attacks and seizures.
Malcolm Lader, a psychologist and pharmacologist at King’s College London in the UK, began studying the benzodiazepine craze as a young scientist in the 1970s. He originally assumed that most people on the drugs had ramped up their dose to such a level that they had become dependant; instead, he found that users had primarily remained on the prescribed dosage.
“People couldn’t believe that you could still be on your original dose…and still have problems when you try to come off,” he recalls.
In the 1980s, Lader and a team of researchers published one of the earliest warnings against long-term benzodiazepine use. Decades of evidence have made clear that taking benzodiazepines comes with dangerous risks, yet they remain hugely popular.
Antidepressants (e.g. Prozac) and cognitive behaviour therapy are powerful anxiety treatments, but neither act quickly; antidepressants can also initially worsen symptoms. For many people, benzodiazepines always seem like the more reliable option.