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Weekly Dose: Valium, the ‘safer choice’ that led to dependence and addiction

Long-term use is not recommended because of the known side effects. But it took two decades, after its release in the 1960s, to recognise this. 3 0 d a g a r m e d a n a l h u s Follow/Flickr, CC BY-ND

Weekly Dose: Valium, the ‘safer choice’ that led to dependence and addiction

Valium is a brand name for diazepam, which belongs to a group of drugs called benzodiazepines. Also included in this class are temazepam, oxazepam, nitrazepam, clonazepam, alprazolam, midazolam and flunitrazepam.

Benzodiazepines remain among the most widely prescribed psychotropic medications – that is, drugs that affect brain function. Nearly 7 million prescriptions are issued for benzodiazepines in Australia each year, with diazepam the most common.

How does it work?

Benzodiazepines bind to specific receptors to strengthen the effect of an amino acid called Gamma-aminobutyric acid (GABA) in nerve cells. This reduces the turnover of other neurotransmitters, therefore depressing the central nervous system.

The dampening of the nervous system reduces anxiety and causes muscles to relax. This leads to sedation, reduced cognition and motor function, and sleep.

Benzodiazepines, like alcohol, are depressant drugs. These are sometimes referred to as “downers” as they make people feel relaxed, sleepy, less coordinated and generally slowed down.

How is it used?

Benzodiazepines have been used for insomnia, anxiety, reducing muscle tension and other situations where there is a need to calm the central nervous system.

There is little controversy about using benzodiazepines in acute psychiatric emergencies, anaesthesia, intensive care, palliative care at the end of life, and in the treatment of seizures and alcohol withdrawal. But its use in long-term situations has been increasingly questioned.

Diazepam is an effective and low-cost drug – at A$11.67 to $17.19 for a pack of 50 in Australia – and therefore remains on the World Health Organisation List of Essential Medications.

Side effects

Benzodiazepines can cause confusion, cognitive impairment and falls, resulting in considerable disruption and socioeconomic costs. This is particularly problematic given that use is more common among older age groups.

Benzodiazepines are also sold as street drugs, can impair driving and are associated with overdose.

Continued use even at low dose for a few weeks can lead to physiological dependence (tolerance and withdrawal). Tolerance means that, over time, the effect of the drug wears off and a higher dose is needed for the same effect. When the drug is stopped, users can experience severe withdrawal symptoms such as insomnia, irritability, tension, panic attacks, tremor, sweating, poor concentration, nausea, palpitations, headache, muscle aches and sometimes even seizures and psychotic reactions.

Long-term use is generally not recommended because of the known side effects.

But withdrawal can be difficult since the initial symptoms for which the drug was prescribed might return, made worse by the symptoms from the withdrawal itself. Some people are therefore reluctant to stop the drug. For these reasons, withdrawal should be gradual and guided by clinicians, who can help patients cope with any symptoms.

History

Up to the mid-1950s, barbiturates were widely used to treat insomnia and anxiety. But the incidence of dependence, severe withdrawal reactions, overdose and death had become a great concern.

In the quest for a safer alternative, American chemist Leo Sternbach created the first compound in the benzodiazepines class of drugs, methaminodiazepoxide.

This led to the release of diazepam (Valium) in 1963, considered to be safer than barbiturates. Over the next decade, it became the most prescribed drug in the United States.

Negative effects were slow to be recognised and widely acknowledged. This took nearly two decades after the description of the withdrawal syndrome. Only then did prescription rates begin to fall.

The good news is there is now greater caution and questioning about the potential unintended effects of new drugs.

Current use

Despite the clear evidence and widespread acceptance that benzodiazepines cause harm, they have a legitimate place in therapeutics, such as in acute emergencies.

Yet despite international and national guidelines recommending that the use of benzodiazepines should be limited to two to four weeks, these drugs continue to be prescribed beyond these time frames.

The reasons for this are complex. As the largest medical workforce, GPs have the greatest contact with patients and therefore prescribe the most medications. They are often seen as responsible for the benzodiazepine problem.

But GPs may not always be the initiator. They often take over the care of patients who have been started on benzodiazepines by psychiatrists or during hospital admissions. Psychiatrists commonly prescribe these medications as an add-on to antidepressant treatment to reduce anxiety and to increase the likelihood that patients will adhere to treatments and respond early.

In Australia, the modest decline in the amount of benzodiazepines prescribed between 1992 and 2011 reflects an awareness of risks and GPs’ reluctance to prescribe the drugs, especially to those who have not previously had them.

Today there is a broad spectrum of people and contexts where benzodiazepines are used, from the clearly legitimate short-term situations in known patients to deliberate drug misuse and sale in people with chaotic and sometimes aggressive behaviour.

GPs are aware that benzodiazepines may be obtained through deliberate “doctor shopping” to obtain medications from multiple medical practitioners under false pretences.

Further, with an increasingly internationally networked world, benzodiazepines can now be purchased on the internet without a prescription.

The promotion of the dangers of inadequate sleep also results in people seeking medications to reach the goal of seven to nine hours of sleep. In some cases, there are underlying causes that can be treated or healthy sleep habits can improve sleep. In other cases, a person may feel well and simply need less sleep.

New guidelines now recognise individual variations with a broader range of possible appropriate sleep durations of six to ten hours in adults aged 26-64 years, and five to nine hours in those aged 65 years and over.

Clinicians need to discuss the potential side effects of sedative drugs with patients, emphasising the risk of dependence and cognitive decline. They also need to promote non-drug approaches for managing stress, insomnia and anxiety, such as cognitive behavioural therapy, and reinforce that sedative drugs do not work in the long term.