« back · www.benzo.org.uk »


Beat The Benzos Index Page

Croydon, UK, November 2000

Neurobiological and Structural Changes
in Benzodiazepine Users

Professor Stefan Borg
Head of Addiction Medicine
Karolinska Institute, Sweden

As Professor Ashton said, I will share with you some of the results from our studies on benzodiazepine dependent patients. We started in 1980 - about 25 years ago, as the number of dependent patients in this area increased and we started to look at admissions and found that about 3% of admissions to psychiatric units at that time had a benzodiazepine dependency diagnosis and no other addiction. When we added the other addictions we came up to 12 - 15%.

We found when we looked at purely benzodiazepine-addicted patients that most of them had a high social incompetence. Less education, *** for instance than other patient groups, but still, the results of our treatment were quite bad. A high percentage of relapses, high mortality - mostly suicides. So we started to think how to manage this situation and we went on some study visits here in the UK, looking at different patient organisations like Tranx and others and found that they treated themselves in a better way than we as doctors treat our patients *** so we developed a long-term tapering programme and we used a scientific model to evaluate it, so the patients who came to us were randomly selected, one control group and one treatment group and after initial investigation they were in hospital care between 2 to 8 weeks where they were tapered and then were followed for one year in an outpatient care situation.

We did a lot of toxicological screening to get the *** information and we also had the opportunity to do investigations like EEG etc.

[Slide 1]

These are the types of drugs that the patients were using and they show exactly the way of [sales* figures*?] in Sweden at that time. So the patients followed the general trend in drug taking.

[Slide 2]

Here we can see the outcome from this treatment programme. In the treatment group, 31 of our patients were free from benzos and 6 were not. In the control group, 5 were free from benzos and 22 were not free. The control group had to go to an ordinary psychiatrist or a general practitioner *** so they were not defeated ***.

So by using the long-term tapering procedure we were able to improve the prognosis quite dramatically in our patient groups.

[Slide 3]

Here are some figures of how the patients felt during the contact with us. You can see that before tapering 62% had concentration problems, 44% decreased memory capacity, 28% fatigability and 22% indecisiveness.


This is during the programme - here they are tapered, you can see that some of the figures are better, but still very high figures for this type of symptoms. So the patients are not much better after being off [the benzodiazepines].


This is one week off drugs, 6 weeks, 50 to 60 weeks off drugs, you can still see quite high figures with these types of symptoms. And here we are coming back to 50 weeks, that's one year off drugs and then we are coming down to more normal figures and you can see that much is happening during the last 6 months of this observation period. So the message is quite clear here it takes a long time to change the psychiatric and cognitive symptoms.


This is the same type of figure and you can see we have the global score of illness, of sleep disorders, sadness, excited, autonomic disturbances. Here we have the Newcastle Index with visual perception disturbances and auditory perception symptoms. You can see the same trend here that shortly after tapering there are very high figures, even higher than when patients started coming to us (starting their tapering).

When we looked in more detail at these symptoms we could identify different types of patterns: the first one here just going down all the time, here you have pessimistic thoughts etc. The second pattern coming up, then going down with a peak quite soon after tapering and third pattern here with a late peak and the last pattern no significant difference at all the time. This is *** showing this in another way, four different patterns.


Now we are going over to some cognitive symptoms: decisiveness, fatigability, concentration ability and memory ability. You can see that the impairment of these is starting up here quite high and then slowly going down during the total observation period and also it's evident that here, the last six months of the observation period it's happening the most for the patients, also stressing the long-term [effects?] for the patients. These were symptoms that were reported to us to the *** we also made a more objective investigation with different neuropsychological tests, you can see here, the test battery, this is synonymous, this is a typical test that is not very sensitive to 'brain dysfunction' and as you can see here:


This is the first investigation and this is one year off abstinence and these are the patients who are on continuous treatment, they have not been able to get off their drugs and these are on withdrawal. You can see that they are about the same - these three groups, but when you come down to the more neuropsychological-sensitive tests, like the block design test you can see the differences. The controls, the steady state ones and the withdrawals. Both the steady state and the withdrawals are increasing. They are less impaired after one year but the patients who are in withdrawal are the ones who show a significant difference.


This is the global score of neuropsychological impairment in our patients. Here you have the patients who have gone through withdrawal, the controls and the steady state group.

So our conclusion was that a high number of our patients - about two thirds were impaired when they came to us and after treatment this decreased and it decreased more in patients who were more successful in their treatment.

We haven't been able to follow up these patients with neuropsychological testing. However we have an impression that this improvement is going on for a number of months and maybe years afterwards. Some patients have reported that they are improving over time, for two, three or four years and we share that impression with Professor Ashton.

What we are doing just now is working on ways to improve the withdrawal/tapering process and we have used a drug for this called flumazenil, which is an antagonist to benzodiazepines and works via the benzodiazepine receptor complex. We have injected this drug into patients and compared them with controls. As you can see here:


This is the patient group and this is the control group and the patients are reporting more symptoms than the controls of course. But when the patients get their flumazenil, the negative symptoms decrease. When the controls get flumazenil their negative symptoms increase so the groups are similar in the end here.

This shows that it would be possible to use this drug, a non-addicting drug, to decrease the symptoms during withdrawal, especially the long-term withdrawal symptoms. All these patients have been off drugs for several months. It would also be possible to use this as a test if the patients are reporting negative symptoms like anxiety etc you could use flumazenil to help you to understand whether a symptom is drug-related. If the symptom is drug-related it should decrease, if it is not there should be no difference in the patient.

That is where we are just now in our research and trying to help our patients in Stockholm. Thank you.

[Note: This speech was transcribed from a recording. Breaks etc in the recording are indicated by ***.]

Biographical Note

Professor Stefan Borg, M.D., Ph.D.

Stefan Borg, M.D., Ph.D., Associate Professor at the Karolinska Institute and Head of Centre for Dependency Disorders at Karolinska and St Goran's Hospitals.Research on different aspects of benzodiazepine dependence since early 1970s and developed a unit for treatment of dependency of benzodiazepines since early 1980s. This unit treats 200-250 patients each year.In connection with the unit research on clinical conditions, psychological functioning during acute and protracted withdrawal and outcome have been studied and published in scientific journals.

Beroendecentrum Nord
Box 125 60
Telephone: + 46 8 672 14 50 or 672 14 51
Fax: + 46 8 672 19 12 or 672 19 04
Email: stefan.borg@cspo.sll.se

« back · top · www.benzo.org.uk »