ISTANBUL, TURKEY – Remediation of the cognitive deficits often present in chronic substance abusers offers an exciting new opportunity to treat addictive disorders.
Two approaches are under investigation: computer-assisted cognitive rehabilitation (CACR) using structured exercises to improve cognitive flexibility and, more recently, pharmacologic manipulation of various neurotransmitter systems that are involved in the cognitive impairment, Frank Vocci, Ph.D., said at the annual congress of the European College of Neuropsychopharmacology.
Findings from numerous studies have established that although vocabulary and verbal skills are preserved in substance abusers, deficits in many other areas of cognition are common.
“The deficits have a high prevalence and are oftentimes as severe as those seen in traumatic brain injury,” said Dr. Vocci, corporate president of the Friends Research Institute, Baltimore.
“They evolve over an extended period of time. They usually go unrecognized by providers. You can't tell who's cognitively impaired based upon a clinical interview; you have to run neuropsychologic batteries. And the patient behaviors are often attributed to personality and character, not cognitive impairment,” he said.
This misinterpretation of cognitive dysfunction as a fixed characterologic issue often sets up a poor therapeutic alliance and patient/therapist mismatch.
The therapist views the substance abuse patient as unmotivated to participate fully in the learning experience, which cognitive-behavioral therapy or its variants are supposed to be.
Cognitive impairment has been shown to be adversely related to treatment engagement. In turn, treatment engagement is related to length of stay in a treatment program, which in turn is strongly related to treatment outcome, he continued.
The cognitive impairment will gradually improve spontaneously during the first 6 months or so of sobriety. But treatment programs in the United States are becoming shorter, which means that patients may not be in treatment long enough to achieve significant cognitive improvement.
“Spontaneous recovery may be too little, too late to be of any real consequence,” according to Dr. Vocci. “We end up with a terrible mismatch: The greatest amount of therapy may be given at a time when a person is cognitively impaired and has the least ability to learn from it.”
This is the impetus for accelerating cognitive recovery.
The initial success came with CACR. William Fals-Stewart, Ph.D., and his colleagues at the State University of New York, Buffalo, Research Institute on Addictions showed in the late 1990s and early part of this decade that CACR that had been designed to address attention, memory, executive function, and problem-solving skills led to improvement in multiple cognitive domains in participants in a 6-month residential recovery program.
In a study involving 120 patients, those who were randomized to three 50-minute CACR sessions per week for 2 months in addition to standard treatment stayed in the treatment program for an average of 200 days, which was significantly longer than the 128 and 132 days in two control groups.
And CACR made a real difference in treatment outcomes: The CACR group had more than twice the program graduation rate, fewer subsequent problems in employment, better family and social functioning, and less medical problems, all of which were fully mediated by the differences in length of stay in the treatment program, Dr. Vocci explained.
However, most of the work with CACR has been done in residential treatment settings, which are becoming increasingly rare. Much research remains to be done before it is known how well CACR will translate to the outpatient setting.
Turning to pharmacologic strategies for accelerating cognitive remediation in substance abusers, Dr. Vocci said that the big news in that regard is that a large, double-blind, placebo-controlled, multicenter randomized trial of modafinil (Provigil) at 200–400 mg/day in methamphetamine abusers has just been completed.
The data of the National Institute on Drug Abuse–sponsored study are now being analyzed in preparation for presentation of the results in 2010.
“This trial is the paradigm shift–looking at medications to enhance cognition in order to enhance treatment,” he observed.
Beyond modafinil, numerous other pharmacologic agents are under study in pharmacology laboratories as selective modulators of a multiplicity of neurotransmitter systems that are believed to play key roles in the cognitive deficits characteristic of substance abusers.
An example is attentional set shifting. In animal models, attentional set shifting can be remediated with use of the veterinary alpha2 noradrenergic antagonist atipamezole (Antisedan), as well as by D-1 dopamine agonists, D-4 dopamine antagonists, or 5-HT6 antagonists. So there is a rich pipeline for pharmacologic remediation of cognitive impairment as a means of enhancing the treatment of addictive disorders.
Some members of the audience commented that they thought giving a psychoactive stimulant such as modafinil to substance abusers sounded somewhat risky.