Yet each condition has a malign influence on the course of the other, increasing the severity of symptoms, reducing compliance, and raising the risk of relapse or rapid cycling. So an integrated approach to treatment is worth pursuing, argued both Professor Alan Green (Geisel School of Medicine, Dartmouth, New Hampshire USA) and Professor Ihsan Salloum (Miller School of Medicine at the University of Miami).
This case is strengthened if a common neurobiological basis can be substantiated – in which case it would be logical to treat the related conditions at the same time, and perhaps even with the same drugs. But this is a prospect for the future rather than a present reality.
Somewhere between 30 and 50% of patients with bipolar disorder and a third of patients with schizophrenia also have an AUD. Of people seeking AUD treatment, a third suffer from anxiety, and perhaps 40% a disorder of mood.
Whichever way we look at it, and whichever way the causal arrows point, the overlap between drug abuse and psychiatric problems is massive. The co-existence of these comorbidities in so many patients raises the question of whether they share a linked pathology.
There is some evidence that this lies in abnormalities in mesocortical and mesolimbic brain reward circuitry involving the opioid peptides and dopamine, Professor Green told the meeting.
It is possible that certain drugs (perhaps atypical antipsychotics in the case of schizophrenia, and anticonvulsants in the case of bipolar disorder) could have beneficial effects on both. Development of such hybrid drug strategies is something for the future, and probably beyond the reach of available drugs, but preliminary efforts are under way.
Worldwide, 76 million people suffer from AUD. It is second only to unipolar mood disorders in the extent of lost quality-adjusted life years. But it is a heterogeneous and complex disease that may involve dozens of different phenotypes. Among the neural systems implicated are those mediating reward, regulation of stress and affect, motivation, executive function, impulse control and the perception of social cues.
There is variability too in what people with AUD want out of treatment. In one recent randomised phase II study, only around a quarter of the two hundred patients enrolled had total abstinence as their aim. The majority wanted to restore control to their drinking but not to give up entirely.
With such biological and motivational diversity, no one approach will work for everyone, and there is a role for both behavioural and pharmacological treatments.
On average, CNS drugs take more than four years longer from discovery to licensing than their non-CNS counterparts. And only 8% of CNS agents entering phase I trials make it to market.
Although there are still few drugs licensed for AUD, there is no shortage of development leads, with the potential molecular targets listed by Raye Litten (Associate Director of the National Institute on Alcohol Abuse and Alcoholism , NIAAA) including the glutamate, opioid, nicotinic acetylcholine and GABA receptors. Their systematic exploration requires a focused approach involving validated animal and human laboratory models.
It also requires the recruitment of expert sites to co-ordinate clinical trials. The newly-constituted NIAAA Clinical Investigation Group (NCIG) aims to complete a clinical study within two years.
The successful development of new anticonvulsants provides a useful precedent. With AUD agents, this is very much a work in progress. But we have to start somewhere.
The alcohol preferring P rat has a genetic propensity to drink. In addition to such models of self administration, chronic exposure to alcohol vapour creates a model of withdrawal. But such techniques require standardisation of strain and methodology.
In man, MRI shows areas of activation related to reward pathways that light up with exposure to alcohol cues. There are drugs that seem able to prevent that.
But it would also be of great help if we had ways of predicting AUD sufferers who were likely to respond to specific pharmacological interventions. There is preliminary evidence that certain genetic and proteomic variations (the latter related to immune and inflammatory system pathways) may assist with this.