The treatment of anxiety disorders, particularly panic disorder, should emphasize behavioural and cognitive therapy, exercise, lifestyle factors, etc.
But medication treatments can often be very helpful if these other therapies are not helping. The trend of thinking on this matter over the past few decades has been to preferentially use SSRI antidepressants, and to minimize the use of benzodiazepines such as clonazepam, due to concerns about side effects and dependence.
This study challenges that notion: http://www.ncbi.nlm.nih.gov/pubmed/22198456 It is a 3 year followup study (an excellent duration for a psychiatric study!) -- and compares paroxetine 40 mg/d with clonazepam 2 mg/d (all doses taken at bedtime) for treatment of panic disorder.
The clonazepam alone group did very similarly well to the paroxetine group, with even a slight edge of superiority over paroxetine. And there were fewer side effect complaints in the clonazepam group compared to paroxetine. There was no advantage to combined therapy (clonazepam + paroxetine).
While I still remain concerned about dependency and abuse problems with benzodiazepines, this type of study affirms that long-term benzodiazepine use may be helpful--and possibly superior to antidepressants--for some patients.
Wednesday, January 9, 2013
Interesting Augmentations 2: L-methylfolate
L-methylfolate is an active form of folic acid which enters the brain. Folic acid supplementation has been considered for decades in treating depression, with varying results (generally mildly positive). The mechanism in the brain is generally as an indirect enhancer of the production of neurotransmitters, through its involvement in the metabolic pathway.
Here are some recent studies looking at l-methylfolate as an augmentation:
http://www.ncbi.nlm.nih.gov/pubmed/21311704
Here, a dose of 15 mg/day of l-methylfolate (but not 7.5 mg) added to an SSRI led to a doubling of the response rate for depressed patients, after 30 days (about 30% vs. 15%). These patients had previously been on the same SSRI alone without response. There were no side effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/23212058
Another positive study from 2011. Again showing a significant improvement in response rate with l-methylfolate augmentation, with no side effect problems (probably fewer side effects in the folate group). But this is a much weaker study due to it being retrospective.
As I look further at this I see some controversy about whether there may be bias here, as the methylfolate is quite an expensive product. I would want to see a comparison study between methylfolate and the much more inexpensive ordinary folic acid. In discussions I've looked at pertaining to this issue, the argument is made that the dose of ordinary folic acid would be very high to match 15 mg of l-methylfolate. Maybe so--but it would be very simple to do a comparison study, since if there is no clinical superiority of one over the other, then the more affordable product should be recommended.
Here are some recent studies looking at l-methylfolate as an augmentation:
http://www.ncbi.nlm.nih.gov/pubmed/21311704
Here, a dose of 15 mg/day of l-methylfolate (but not 7.5 mg) added to an SSRI led to a doubling of the response rate for depressed patients, after 30 days (about 30% vs. 15%). These patients had previously been on the same SSRI alone without response. There were no side effect problems.
http://www.ncbi.nlm.nih.gov/pubmed/23212058
Another positive study from 2011. Again showing a significant improvement in response rate with l-methylfolate augmentation, with no side effect problems (probably fewer side effects in the folate group). But this is a much weaker study due to it being retrospective.
As I look further at this I see some controversy about whether there may be bias here, as the methylfolate is quite an expensive product. I would want to see a comparison study between methylfolate and the much more inexpensive ordinary folic acid. In discussions I've looked at pertaining to this issue, the argument is made that the dose of ordinary folic acid would be very high to match 15 mg of l-methylfolate. Maybe so--but it would be very simple to do a comparison study, since if there is no clinical superiority of one over the other, then the more affordable product should be recommended.
Tuesday, January 8, 2013
Interesting Augmentations 1: creatine + SSRI
From my annual review of articles from psychiatry journals, here is the first of a few which caught my eye: they're very simple studies looking at medication augmentations.
An augmentation refers to adding some type of therapeutic agent (usually a medication) to help make another therapeutic modality work better. Usually an augmentation would not be expected to help much on its own--the term implies that it must be used with something else. Typical augmentations in common use are triiodothyronine (a form of thyroid hormone) or lithium added to antidepressants to treat depression.
It's always nice to see an article which has an extremely simple premise (e.g. to try some new therapy or other), which could be readily applied in an attempt to help someone immediately.
The first article is from a Korean group (Lyoo et al.) published in the American Journal of Psychiatry in September 2012. ( http://www.ncbi.nlm.nih.gov/pubmed/22864465 ) They looked at treating 52 women having a major depressive episode, with either escitalopram 10-20 mg/day plus placebo, or escitalopram 10-20 mg plus 5 grams of creatine monohydrate daily.
From the second week of treatment onwards, the creatine group had better symptom improvement. After 8 weeks, over 50% of the creatine group met criteria for remission, compared to only about 25% of the placebo group.
Creatine has been used for years as a type of muscle-building supplement. It may have some benefits for various neuromuscular and other neurological disorders. Risks and side-effects are minimal, according to my reading of existing evidence, particularly at doses of 5 grams per day or less (see this risk assessment review: http://www.ncbi.nlm.nih.gov/pubmed/16814437 ). In the brain, the mechanism is of improving ATP availability, thereby improving cellular energy dynamics. Humans obtain creatine from the diet (about 1 g/day) and from synthesis inside the body (another 1 g/day). So it makes sense to have therapeutic doses well above the body's baseline supply of 2 g/day. Here is a reference to an excellent review article by Persky (2001 http://www.ncbi.nlm.nih.gov/pubmed/11356982
Creatine is readily available wherever one would obtain nutritional supplements. If one were to try creatine, I might suggest looking for pure creatine monohydrate, as opposed to some mixture (typically with protein powder), as the mixture would be more expensive, and would often contain unnecessary additives such as artificial sweeteners. The creatine could be ingested as a partially dissolved suspension in warm water or juice. The dosing regime could be debated somewhat, as creatine has quite a short half-life in plasma. This current study used a single large dose daily, but the idea of using divided dosing should be explored.
An augmentation refers to adding some type of therapeutic agent (usually a medication) to help make another therapeutic modality work better. Usually an augmentation would not be expected to help much on its own--the term implies that it must be used with something else. Typical augmentations in common use are triiodothyronine (a form of thyroid hormone) or lithium added to antidepressants to treat depression.
It's always nice to see an article which has an extremely simple premise (e.g. to try some new therapy or other), which could be readily applied in an attempt to help someone immediately.
The first article is from a Korean group (Lyoo et al.) published in the American Journal of Psychiatry in September 2012. ( http://www.ncbi.nlm.nih.gov/pubmed/22864465 ) They looked at treating 52 women having a major depressive episode, with either escitalopram 10-20 mg/day plus placebo, or escitalopram 10-20 mg plus 5 grams of creatine monohydrate daily.
From the second week of treatment onwards, the creatine group had better symptom improvement. After 8 weeks, over 50% of the creatine group met criteria for remission, compared to only about 25% of the placebo group.
Creatine has been used for years as a type of muscle-building supplement. It may have some benefits for various neuromuscular and other neurological disorders. Risks and side-effects are minimal, according to my reading of existing evidence, particularly at doses of 5 grams per day or less (see this risk assessment review: http://www.ncbi.nlm.nih.gov/pubmed/16814437 ). In the brain, the mechanism is of improving ATP availability, thereby improving cellular energy dynamics. Humans obtain creatine from the diet (about 1 g/day) and from synthesis inside the body (another 1 g/day). So it makes sense to have therapeutic doses well above the body's baseline supply of 2 g/day. Here is a reference to an excellent review article by Persky (2001 http://www.ncbi.nlm.nih.gov/pubmed/11356982
Creatine is readily available wherever one would obtain nutritional supplements. If one were to try creatine, I might suggest looking for pure creatine monohydrate, as opposed to some mixture (typically with protein powder), as the mixture would be more expensive, and would often contain unnecessary additives such as artificial sweeteners. The creatine could be ingested as a partially dissolved suspension in warm water or juice. The dosing regime could be debated somewhat, as creatine has quite a short half-life in plasma. This current study used a single large dose daily, but the idea of using divided dosing should be explored.
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