4 July 2021

Benzodiazepines in psychiatry and addiction medicine - do they still have a place in chronic care?

Sydney Addiction Seminar

Wednesday 28th November, 2018

“Benzodiazepines in psychiatry and addiction medicine - do they still have a place in chronic care?”

Vladan Starcevic, Paul Haber, Andrew Byrne. Moderator Dr Richard Hallinan.

 

Psychiatrist and Associate Professor Vladan Starcevic spoke about the safety and effectiveness of diazepam and related drugs for anxiety.  He stressed the poor results from almost every treatment tried since the time of Hippocrates for this common and disabling condition.  This changed dramatically with the introduction of benzodiazepines starting with chordiazepoxide (Librium) in 1959.  We were shown numerous trials which included comparisons with tricyclic antidepressants, SSRI’s, SNRI’s and non-drug alternatives (talking therapies, yoga, acupuncture, etc).  The benzodiazepines came out as more effective nearly every time.  The speaker emphasised the low rates of side effects (‘almost none’) as well as the low rates of dependence on the drugs (around 2% in most studies).  It seems that sedation is not considered a side effect of sedatives but a dose related effect, sometimes wanted, as for insomnia, or unwanted for daytime anxiety patients. 

Some myths were busted such as the canard that antidepressants are not habit forming, do not develop tolerance and do not have any withdrawals (further supportive studies were cited).  The saga of the use and alleged abuse of fluoxetine (Prozac) was quoted.  Professor Starcevic almost sounded like an advertisement for benzodiazepines yet he is clearly expert in the field and quoted rigorous studies to support his views.  He also serves on a number of international committees on the treatment of anxiety and related disorders.  We have all seen the pendulum swing from Valium and related drugs being the panacea to the pariah.  Despite this prescribers all know the great benefits which can be had by using careful assessments, judicious prescribing with psychosocial supports for stress cases who can be very vulnerable and for whom there are few effective alternatives. 

 

This led into a talk by Prof Haber of some aspects of pharmacology of GABA receptors and the respective places in the neurone where barbiturates, alcohol, benzodiazepines, etc, were thought to act … and how flumazanil can block the process of hyper-polarisation when chloride ions are allowed into the cell making it less likely to depolarise.  Then Prof Haber reminded us of the origin of the suffix ‘PAM’ attached to so many of the benzodiazepines - and said it might be the only thing some audience members might remember from the whole evening.  Positive Allosteric Modulators (PAM) of the neurone.  We were shown slides from PBS to demonstrate the enormous popularity of sedatives in Australia since the benzodiazepines replaced the barbiturates from about 1960 onwards. 

 

I spoke next about our negative experience using the zero-tolerance approach.  This had resulted in many patients relapsing after periods of benzodiazepine reductions or abstinence, often associated with high potency products such as alprazolam, clonazepam or flunitrazepam (Xanax, Rivotril, Hypnodorm).  These were sometimes prescribed but most commonly were obtained from the street market.  We selected some long-term patients who were clearly benzodiazepine dependent and allowed a limited daily dose, initially under supervision.  This was most usually diazepam in doses from 2mg to 15mg daily. 

American treatment guidelines point out that just because a patient in on OTP they should not be denied benefits of benzodiazepines for anxiety, panic disorder, insomnia or epilepsy.  And those with dependency need to have this addressed.  Yet this should not simply mean “Valium on demand”. 

I was asked whether I was treating dependence or psychiatric symptoms of stress and anxiety: which is almost like the question of which came first, the chicken or the egg?  Just as methadone maintenance patients may comprise pain management cases as well as some recreational drug users, the matter becomes academic once the patient gets to a certain point in their opiate consumption.  It is now widely agreed that whether one started drug use in a medical setting or the illicit market, opiate dependency treatment should be the same. 

Withdrawal symptoms from both opiates and benzodiazepines usually involve dysaesthesia, anxiety and/or insomnia.  Hence it is not surprising that for some OTP patients, the consumption of opiates and benzodiazepines is closely aligned and equally important to them. 

We have long used the principles of ‘universal precautions’ which assumes that all patients are potentially dependent and should be treated as such, with some dose supervision, some counselling and occasional urine toxicology testing.  Equally, all patients may be genuine anxiety disorder sufferers and thus deserve consideration of pharmacotherapy for that just like any other medical or psychiatric patient.