N-acetylcysteine for OCD

I've written a post about N-acetylcysteine before (http://garthkroeker.blogspot.ca/2009/09/n-acetylcysteine-for-treatment-of.html), which suggested that it could be useful in treating compulsive behaviour disorders such as skin-picking. 

A recent 2012 study by Afshar et al. has shown that NAC is useful for treating obsessive-compulsive disorder (OCD).  Here's the reference: http://www.ncbi.nlm.nih.gov/pubmed/23131885

In this study, 48 patients with OCD who had not responded to an SSRI were given NAC up to 2400 mg/day or placebo, in addition to a continued dose of the same SSRI, for 12 weeks. 

The NAC group had about a 40% reduction in YBOCS score (a quantitative measure of OCD symptoms) after 12 weeks, compared to a 20% reduction in the placebo group.  This is a good, clinically relevant symptom change especially for a treatment-resistant group. 

Mild gastrointestinal complaints were more common in the NAC group, but there was not a big difference in drop-out rates between placebo and NAC. 

NAC works as as a glutamate-modulating agent, with possible anti-inflammatory effects.  It is metabolized to the amino acid cystine after entering the brain. 

So it appears that NAC could be a simple, low-risk, effective adjunct, or even a primary treatment modality, for obsessive-compulsive disorder. 

I would be curious to see more research looking at NAC for other anxiety disorders, or for ruminative depression. 

Doidge (Neuroplasticity) review - part 3 (Schwartz)

Doidge devotes a chapter to discussing obsessive-compulsive disorder. He claims that a treatment developed by Jeffrey M. Schwartz is "plasticity-based". The implication is that other psychological treatments for OCD are NOT "plasticity-based."

Schwartz has published articles in the literature going back into the 1980's looking at OCD patients using PET imaging.

I do not find any good study in the literature about Schwartz's particular technique, as published in his book, in particular no study comparing his technique with CBT.

Also the theory is presented that OCD is caused by a failure for the caudate nucleus in the brain to "shift gears automatically", and that the therapy described is a means of "shifting gears manually." While there are a variety of brain metabolism changes in OCD, I think it is an overly strong statement to believe that this is literally true. One could use the idea of the "caudate gear box" as a metaphor, but it may be quite inaccurate, or at least poorly supported by clear evidence, to be taken literally.

So it concerns me that the chapter in Doidge's book about the "brain lock" approach is more of a book plug than something founded on solid evidence. Doidge could well have made the case that CBT is a type of "neuroplasticity-based treatment". In fact, there is good data to support such a case--including numerous imaging studies--and including a recent paper which Schwartz himself co-authored, which shows various regional changes in brain metabolism associated with improvement in OCD symptoms from intensive CBT:
http://www.ncbi.nlm.nih.gov/pubmed/18180761

Yet, I think it is important to be open about any new therapeutic idea--it may be that the "brain lock" therapy for OCD could be helpful to many people. It's just that Schwartz's book has been given an endorsement by Doidge without a convincing amount of good evidence, while minimizing the robust evidence favouring CBT.

Trazodone

Trazodone is another antidepressant introduced in the early 80's. Once again, its use was fashionable for a time, gradually faded, and at this point it is mainly used adjunctively to treat insomnia.

It is notable among antidepressant choices in not causing sexual side effects (other than the rare incidence of priapism, which is a medically dangerous, painful, abnormally sustained penile erection, which occurs in probably less than 1 in 1000).

The trouble with trazodone is that for many people, it causes too much daytime sedation. However, it can be worth a try, to treat insomnia associated with depression or antidepressant therapy, or possibly as an augmentation to treat depression or OCD.

In my experience, about 50% of people find trazodone a helpful adjuct, but the other 50% find it causes too much tiredness or dizziness the next day to be worth continuing.

Here is a literature review:


http://www.ncbi.nlm.nih.gov/pubmed/19112384
{in this 2008 study from a minor journal, trazodone was shown to increase the amount of slow-wave sleep in treating chronic insomnia}

http://www.ncbi.nlm.nih.gov/pubmed/12930437
{a 2003 urology article showing evidence that trazodone may help treat erectile dysfunction, especially at higher doses}

http://www.ncbi.nlm.nih.gov/pubmed/18978492
{a small 2008 study showing that 50-100 mg of trazodone may reduce SSRI-induced sexual dysfunction}

http://www.ncbi.nlm.nih.gov/pubmed/16968574
{a small 2006 study showing equivalence between trazodone and sertraline in treating depression over 6 weeks}

http://www.ncbi.nlm.nih.gov/pubmed/10507215
{a small 1999 study from a podiatry journal, showing that trazodone can help with painful diabetic neuropathy symptoms}

http://www.ncbi.nlm.nih.gov/pubmed/8010365
{a 1994 American Journal of Psychiatry article showing that trazodone can help with antidepressant-induced insomnia, particularly helping with overall subjective sleep quality, reducing waking in the middle of the night, and reducing early morning waking}

http://www.ncbi.nlm.nih.gov/pubmed/8988452
{this awkardly-designed 1996 study suggests that combination treatment including 100 mg of trazodone may help in treatment-resistant depression}

http://www.ncbi.nlm.nih.gov/pubmed/11518472
{this quite weak 2001 study nevertheless suggests that trazodone helps to reduce nightmares in PTSD patients}

http://www.ncbi.nlm.nih.gov/pubmed/6337131
{an early, 1983 study, of trazodone vs. imipramine for treating moderately to severely depressed outpatients. Despite the weaknesses of the study design, it did have some follow-up over 3 years, showing that trazodone works well for some people, and worked as well as imipramine overall}

http://www.ncbi.nlm.nih.gov/pubmed/18311107
{an example of a small study suggesting that adjunctive trazodone could help improve OCD symptoms. Some studies have shown no anti-OCD effect with trazodone alone, but others have shown trazodone alone to be beneficial in refractory OCD. In any case, I think the evidence base suggests that trazodone could at least be worth a try, either together with an SSRI, or even on its own.}

OCD

Obsessive-compulsive disorder (OCD) is a common anxiety disorder. It is characterized by recurrent, bothersome mental or behavioural habits. "Obsessions" are recurrent, unwelcome thoughts or images, and "compulsions" are habitual behaviours (physical actions or sequences of thoughts) which often relieve the anxiety induced by obsessions. The symptoms can arise at almost any time in life, but often begin during childhood or during young adulthood. The symptoms often wax and wane over time, sometimes changing slightly from one type to another, sometimes becoming worse during stressful situations.

There are certain types of symptoms that are most common:
1) obsessive concern about germs or dirt, leading to compulsive washing
-this pattern can become so extreme that hours of the day can be spent cleaning, hands getting badly chapped from overwashing; there can be a lot of avoidance of situations (e.g. crowds, public transit, washrooms, shaking hands with people) where there may be a perceived abundance of germs

2) obsessive doubt, leading to compulsive checking
-those with this symptom frequently feel that they have made a mistake--sometimes a catastrophic mistake such as having left the oven on, or having hit someone with their car--leading to a compulsive need to go back and check to make sure this hasn't happened. A lot of time can be wasted going back to check and re-check. Often times people with this symptom realize their behaviour is irrational or excessive, but the feelings are so strong that they can't stop the pattern.

3) obsessive or compulsive symmetry: a need to assess the symmetry of things, or to make things symmetric. Sometimes there may be a need to do an activity (e.g. brushing teeth, or tying shoes) in a very particular way, and if something interrupts the behaviour, the symptom makes the person want to go back and start again from the beginning. A related symptom is a feeling of needing to count things in multiples, or do things a certain number of times (e.g. things have to be in threes).

4) obsessional thoughts: often these are thoughts about doing something forbidden or inappropriate; they often have a violent or sexual nature, and can be hard for people to talk about (people can be embarrassed or ashamed at having the thoughts). Symptomatic people often will interpret their thoughts as evidence that they are not safe or that they are losing their mind. The symptom can lead to avoidance of many situations (e.g. if the obsessional thought is about doing something aggressive, it may lead to avoidance of being around other people).

There are many other varieties of obsessions & compulsions, and it can be helpful to read an educational book on the subject. The OCD Workbook by Bruce Hyman is a good example.

There are two types of therapy that help most with OCD:

Cognitive-behavioural therapy is extremely important and has been shown to work. The main principles here are to educate oneself about OCD, to be able to recognize and pronounce the symptoms as they occur (i.e. to recognize in one's mind that "this is an OCD symptom, not a sign of insanity or dangerousness"), to stop oneself from doing the compulsive behaviours, and to practice exposure to situations that induce the symptoms (e.g. for the germ phobic person, the exposure therapy may be spending time with bare hands scooping soil in a garden).

Antidepressant medications which act on the serotonin system in the brain also reduce OCD symptoms.

Typically, any treatment for OCD reduces symptoms by about 30%. For some people the treatments work much better. Often times, combinations of therapy techniques, continued for longer periods of time, are needed to tame the symptoms more completely.