Thursday, November 3, 2011


Piracetam is a so-called "nootropic" drug, a substance which supposedly helps improve cognitive functioning.  It is available without prescription as a sort of supplement in many parts of the world.  In Canada it is not illegal, but must be imported (such as by ordering over the internet from U.S. suppliers).

The mechanism of action is not clear.   There is no obvious single receptor-mediated mechanism.  There may be various effects on ion channels, cell membrane characteristics, etc. but of course such statements are quite vague.

It is quite clear that there are few side-effect problems or toxicity risks with this agent.  Doses are typically 2-5 grams per day.

I became interested in this agent after encountering a case example of someone who reported quite a dramatic improvement in mood and overall functioning attributed to piracetam supplementation.

Here are the results of my survey through the research literature:  -- a 2005 review  -- a 1991 review looking specifically at its use  in treating  dementia; the data is really not impressive at all for dementia treatment.  -- a 2000 Japanese study affirming the effectiveness of piracetam combined with clonazepam  for treating myoclonus  (myoclonus is a neurological problem in which muscles are twitching involuntarily).  -- a 1996 study from Japan also showing benefit in treating myoclonus;  there were also improvements in motivation, attention, sleep, and mood (possibly secondary to improvement in the movement disorder). -- 2001 study from Archives of Neurology again affirming that piracetam is effective over 12 months of follow-up for treating myoclonic epilepsy. -- this 2000 Cochrane review stated that the data on piracetam are inconclusive, with studies not being of good quality - this 1999 article reviewed studies of piracetam for treating vertigo, concluding that it was useful for reducing frequency of recurrence, at doses of 2-5 grams per day.  -- this is a 2007 randomized placebo-controlled study from The Journal of Clinical Psychiatry,  in which piracetam 4800 mg/d for 9 weeks led to substantial improvements in tardive dyskinesia, with large differences from placebo.  -- piracetam has some antiplatelet function, which could be used in managing or preventing recurrences of vascular disorders.  This is a 1999 review of this subject.  -- this is a broad review of nootropics, published in 1994.  -- this 1987 study from The Journal of Clinical Psychopharmacology shows that children treated with piracetam may show improvements in dyslexia.
Doses were 3.3 grams daily x 36 weeks (dosed twice per day).  However, as I look at the results, I see that there is a statistical difference, but the numbers really look very similar between placebo and piracetam.    The placebo group improved substantially; the piracetam group improved only slightly more.  For example, the raw scores in the Grey Oral Reading Test increased from 17.1 to 22.5 in the placebo group; in the piracetam group it increased from 14.8 to 22.9.   It is true that the piracetam was well-tolerated, with minimal side-effect problems.
this is a 2002 study which attempted to show whether piracetam could prevent ECT-induced cognitive problems.   The dose was 7.2 g/day for a 2-week loading phase, then 4.8 g daily for the remaining 2 weeks.  They concluded that piracetam had no effect on cognition in this group; but the piracetam group did slightly better than the placebo group in terms of overall clinical improvement.
this 2006 study described anxiolytic effects of piracetam which were blocked by flumazenil (a benzodiazepine receptor blocker), suggesting that piracetam has some GABA-like activity.
a Hungarian study describing successful use of piracetam to treat alcohol withdrawal delirium
a 1993 Indian study showing that piracetam has anti-anxiety effects when administered on a longer-term basis in rats.
a 1979 article from Journal of Affective Disorders describing anti-anxiety effects from piracetam similar to a benzodiazepine, but without sedation.
in this 1983 study, piracetam 2.4 g/day or 4.8 g/day was compared with placebo in treating 60 elderly psychiatric patients; the 2.4 g/day group showed increased socialization, altertness, and cooperation, and had some improvement on memory and IQ tests, compared to the placebo group.
in this 1977 study, elderly psychiatric patients were given 2.4 g/day of piracetam or placebo, for 2 months.  The piracetam group did not improve in any cognitive tests or mood symptom scores compared to placebo, but interestingly 52% of subjects in the piracetam group showed overall improvement (CGI) compared to only 25% in the placebo group.
a Cochrane review from 2001 concluding that there is evidence that piracetam may improve the course of aphasia after stroke; however, the evidence was found to be weak.
this 1982 study shows that 40 g of IV piracetam caused greater reduction than placebo in antipsychotic-induced Parkinsonian side-effects.
a small 1979 study which showed that refractory depressed patients improved with the addition  of 2.4 g piracetam.
a look at toxicity risk due to piracetam, when given in higher doses (12 g/day) for 12 weeks, to stroke patients.  The paper concludes that there is no significant toxicity risk at this dose for this population.

In conclusion, piracetam appears to be clearly effective for a few uncommon conditions, such as myoclonus.  There is possible effectiveness for some other problems such as tardive dyskinesia.  The evidence for effectiveness as a "cognitive enhancer" appears to be quite shaky, but not absent.

I am particularly interested in some of the evidence which suggests that it could be useful as a safe, well-tolerated adjunct to treat depression or anxiety.  Some of the studies quoted above appear to support this possibility.  This theme also intersects with my recent thoughts about considering cognitive function in chronic mood, anxiety, ADHD, or personality disorders. A weakness in working memory capacity or executive functioning could substantially interfere with recovery from psychiatric illness; I suspect that a treatment which could specifically help with cognitive function could be a unique angle to augment treatments for these other psychiatric problems.  (see my previous post, which discusses an association between rumination & working memory dysfunction:  Here's another link about this:

I do think it would be worthwhile for research groups to consider doing some new, careful, large trials of piracetam as an augmentation for managing depression, anxiety disorders, etc.