Wednesday, December 31, 2014

Internet Addiction

Most of us can understand the phenomenon of "internet addiction."    We can easily end up spending too much time on the internet, or on other electronic gadgets.  An interesting documentary called "Web Junkie," which is set in Shanghai, is a good introduction to the subject.  This documentary also illustrates some interesting elements of therapeutic care in China:  on the one hand, there is sort of an authoritarian, militaristic boot-camp style (epitomized by the doctor who runs the clinic).  Yet on other hand, there are some calm, gentle, patient, quiet therapists shown (such as the one female doctor). 

A recent meta-analysis by Cheng and Lee (*) showed that rates of internet addiction in different countries ranged between 2% and 10%.  Interestingly, rates were lower in countries with a higher quality of life, such as in Western Europe, and rates were much higher in countries with lower quality of life. 

Restriction of children's internet use by parents is associated with lower risks of internet addiction (**).    Low satisfaction with family relationships is a strong risk factor. (***).

Children with ADHD are at particularly high risk for internet addiction, with a strong association between addiction scale scores and ADHD severity scores. (****).  Depression, anxiety, and introversion are also risk factors.    Internet addiction is further associated with other addictive problems, including alcohol dependence and smoking. 

Another study looked at a rating scale called the IMQ-A,****** which assesses motives for using the internet.  The scale is based on the DMQ-R , which looks at a person's motives for drinking.   The highest risk for addiction is for those who are using the internet as a coping device (e.g. "to forget your worries"), while using it for social reasons or for education is less risky.

A recent review by Spada (******) suggests that the treatments thus far are quite straightforward:
 1) management of anxiety, depression, and ADHD symptoms
2) addressing family relationships if necessary
3) simply keeping track of internet use, and limiting it strictly
4) medication trials including antidepressants or stimulants if indicated.  Naltrexone 150 mg/d plus sertraline 100 mg/d was used effectively in one case. (*******).

I would add that basic lifestyle habits, including daily exercise, healthy diet, and a deliberate daily activity schedule (including social visits, work, and leisure), are essential, particularly since compulsive internet use leads to a lot of time spent alone in a sedentary posture. Postures in front of a device are also usually slumped, in a head-forward position, looking downwards.  Aside from physical health problems, this type of posture probably has negative psychological effects.  Standing and walking around regularly, with simple posture exercises, stretching in an extension position, etc. are bound to be useful.  Amy Cuddy's work on posture would be worth checking out--a good place to start would be her TED lectures. 

A few other points:
1) a bright screen should not be used near bedtime, since it will interfere with melatonin secretion, and cause sleep disruption.   An alternative for bedtime reading can be to use a device in which the font is reversed, with dim white letters on a black background. 
2) ironically, the internet can also be a valuable aid to treating psychological symptoms.  Web-based CBT can be nearly as effective as seeing a one-on-one counselor for some problems, and at the very least could be a valuable adjunct.   But the problems lie with spending too much time on-line, such that other aspects of life suffer.    Reward circuits in the brain may be fired up by numerous internet activities, in an exaggerated way, causing a distortion of judgment about the merits of continuing the activity. 

Ketamine for PTSD

Feder et al. (2014) published one of the first studies looking at possible use of ketamine to treat PTSD. * In this study, ketamine (0.5 mg/kg IV over 40 minutes) was compared with midazolam, on a randomized, double-blind basis, to treat PTSD patients.   In a crossover design, each patient was scheduled to receive a second infusion, 2 weeks later, of the drug they had not received the first time. 

I think a particular strength of this study was the use of midazolam as an active placebo.  The study would have been strengthened even further if they asked subjects afterwards to guess which medication they had received (most patients would have been familiar with benzodiazepines, and would have known that they did not lead to lasting improvements in their symptoms--presumably most of the patients would have wanted to receive the ketamine, as a novel, hopeful treatment).

The results appear similar to other studies of using ketamine to treat depression:  significant improvement in the week following the infusion.  The acute dissociative effects of the drug wear off completely within a few hours, as ketamine levels go down to zero during this time, yet the symptom improvements are maximal after 24 hours, and continue to be significant over a one-week period. 

The overall effect was to reduce PTSD and depression symptom scores at least by half, with improvements in all PTSD domains.

Side effects were not a major problem; in the 24 hours following the infusion, ketamine patients reported more blurry vision, restlessness, and nausea, compared to the midazolam patients.  Only one ketamine patient dropped out during the infusion, because he felt uncomfortable with it. 

For the patients who had received ketamine first, 7 of 22 were still responders after 2 weeks, compared to only 1 of the midazolam group. 

Once again, I think it would be useful for more studies to explore oral or sublingual ketamine dosing, since this would be much more convenient and practical for a larger number of patients.  A gradual intravenous infusion over 40 minutes leads to a fairly similar change in serum levels compared to GI absorption.  Rapid bolus dosing is an advantage of using IV, but this has not been used for administering ketamine to psychiatric patients.   There are differences in the ratio of ketamine vs. metabolites with the oral vs. IV routes, but I do not see that the differences are so great as to obstruct the benefits.   Dose finding is less precise with oral dosing, but this is a technical matter which can be simply resolved through careful titration.    In any case, science may answer this question for us, through well-designed trials.  A study design I would suggest for this would be a double-blind crossover study comparing oral ketamine + IV saline infusion   vs. IV ketamine + oral placebo, with one treatment per week for 4 weeks.  Doses could be adjusted according to response and side effects on treatments 2, 3, and 4.

Tuesday, December 30, 2014

Topiramate for Alcohol Use Disorders

Topiramate is an anticonvulsant which has shown some promise for treating a variety of psychiatric problems, including alcohol use disorders, binge eating, compulsive behaviour, and mood instability.  

One recent study, by Knapp et al, published in the February 2015 edition of The Journal of Clinical Psychopharmacology, compared topiramate with several other medications, and with placebo, for treating 85 heavy drinkers ("heavy" meaning over 35 drinks per week, for men).  * The study duration was 12 weeks.  The target dose of topiramate was 300 mg/day. 

Those in the topiramate group ended up having markedly fewer days of heavy drinking, markedly less total alcohol consumption, and reduced measures of craving, compared to placebo. In general, the topiramate group had at least twice as much improvement in these measures, compared to placebo, which was clinically very significant.  

This study was consistent with others, showing that topiramate can be an effective treatment for alcoholism.  **  

Cognitive-side effects (e.g. memory impairment)  are the main problem with topiramate.  So it is interesting to consider whether lower doses could be useful.  Martinotti et al (2014) did a small study showing topiramate 100 mg per day was useful for treating alcohol dependent patients, with a comparable effect size as the study quoted above.    ***

I am interested in topiramate for other problems which feature compulsive behaviour.  There is some promise in OCD, the studies showing mixed results.  In a genetic disorder called Prader-Willi syndrome, which is characterized by obesity, compulsive self-injury, and intellectual handicap, a trial of topiramate led to significant improvements in the compulsive self-injury.  ****   There have been several studies (e.g. *****) showing that topiramate can be of use in treating binge eating or bulimia, at doses similar to those described above.  Topiramate is also a leading preventative treatment for recurrent or chronic migraines, at a dose of 100 mg daily (******).  It is reasonable, then to think of topiramate in the many cases where there are a combination of these problems, for example a patient with recurrent migraines, who also may have binge eating symptoms, alcohol abuse symptoms, or compulsive self-injury. 


Meta-analysis is a powerful technique for summarizing data across many research studies.  For example, to understand the role of psychotherapy or antidepressants to treat depression, a meta-analytic study could give us our best starting point to estimate the effect size.

But the meta-analytic method has a prominent weakness, what I would call dilution:

Suppose that one is doing a meta-analysis of the effectiveness of surgery vs. supportive care for treating abdominal pain.   Many studies might show that surgery is remarkably effective, yet others would show no difference, or even a negative effect, compared to supportive care.  The meta-analysis could average these out, and conclude that there was little difference.    The reason for the dilution is that there are some specific types of abdominal pain, with specific causes, which are best treated surgically (e.g. appendicitis).    Many other types of abdominal pain settle down on their own, or require simple supportive measures.  In the past, it was often difficult to determine whether a patient definitely had appendicitis or not, in the early stages of the illness.   Therefore there would have been many unnecessary appendectomies, and many other cases of ruptured appendicitis operated on too late.

Similarly, in psychiatry, I think it is probably true that there are particular subtypes of depression (or other diagnoses), which respond much better to psychotherapy, or much better to a particular medication, or which might settle down completely on their own with no help at all.   At present, our diagnostic schemes do not help us very much to differentiate between these groups.  We often assume that mild depressions are best treated with psychotherapy, and severe depressions are more likely to need medication treatments.  While there is evidence that supports this assumption, it is not invariably true:  some cases of mild depression persist for long periods of time, do not improve with psychotherapy, but may improve dramatically with a medication trial.  Conversely, some severe cases of depression may not respond well to medications, but improve dramatically with psychotherapy (sometimes a very particular type of psychotherapy).

An ongoing area of research must be to improve our ability to predict the optimal treatment strategy.  I suspect that in most cases, this strategy will involve some combination of psychotherapy, medication, and practical social support.    I think that the science to help us in this task is more likely to come from genetics, and less likely to come from more sophisticated questionnaires or symptom scales.

The search for these answers is confounded, in psychiatry, by a very high risk of placebo-like psychological effects, which must be addressed by studies which have very careful placebo controls and active placebo controls.

For example, many patients are understandably attracted by a very "high-tech" or "advanced science" approach to treating their illness.  So we have some clinics which offer sophisticated technology, such as neurofeedback, PET imaging, genomic analysis, etc.  While these technologies are interesting, and possibly very useful, they also carry a sort of "guru effect."  A PET scan yielding exciting images showing metabolic changes in the brain, accompanied by a detailed diagnostic report, could be much more persuasive than reading the exact same report without the images.    Therefore the PET imaging could act as a marketing tool, to cause the person to take the report more seriously, irrespective of whether the imaging actually shows something of true scientific relevance.  It would be like visiting a fortune-teller, but receiving actual images of your brain which are referred to in the fortune-teller's predictions about you.   It would be especially convincing!    Similarly, with neurofeedback, the dazzle of the technology could cause people to take the therapeutic tasks more seriously, causing improvement separate from the independent benefit of the technique.   I am particularly concerned about the risk of bias with these techniques, because some clinics or private practitioners are charging very high fees for patients to have them.  This is an environment in which selective glowing testimonial accounts could distort a reasonable summary of the data.

In order to conduct research properly with these new modalities, we must have very careful active placebo groups.  In a neurofeedback study, for example, there should be sham neurofeedback which generates a similar type of interactive therapeutic task, with a similar degree of technological dazzle. 

Wednesday, December 17, 2014

Intensive vs. Regular CBT for PTSD

Ehlers et al. published a good study in the March 2014 edition of The American Journal of Psychiatry in which they compared the following treatments for PTSD:
1) 3 months of regular weekly CBT
2) 7 days in a row of intensive CBT (up to 2 hours daily)
3) 3 months of weekly supportive therapy
4)  waiting list control

They found similar good treatment results, after 40 weeks of follow-up, in the regular CBT and the intensive CBT groups, with a slight edge for better response in the regular CBT group.  Total remission in symptoms occurred in 50-70% of these groups, compared to only 30% in the supportive therapy group, and no change in the waiting list group.

Once again, a weakness in these CBT studies is a failure to account for the amount and quality of homework done.  Possibly the regular CBT group had more frequent reminders to keep up with homework tasks and exposure activities, which is a reason why they did slightly better than the intensive CBT subjects. 

What I take from this study is, first of all, CBT techniques (or related techniques which involve similar practice and exposure) are imperative, regardless of other supportive techniques also used. 

Second, I think there is a role for both intensive CBT and longer-term weekly CBT.  It could be useful to have a regular course of CBT with at least one week of intense weekly sessions as well.  It reminds me of any other skill to learn, such as learning a foreign language, learning to swim, learning a musical instrument, etc. :  regular lessons are great, but an intensive week-long program could give you a huge boost, in terms of skills, habit-building, and interested devotion to the work.  In both of these cases, much of the progress will be a result of diligent daily practice and homework, over a period of months.