Nootropic and smart drugs

Aphasia, the loss or impairment of language caused by brain damage, is one of the most devastating cognitive impairments of stroke. Aphasia is present in 21-38% of acute stroke patients and is associated with high short- and long-term morbidity, mortality and expenditure. Recovery from aphasia is possible even in severe cases. While speech-language therapy remains the mainstay treatment of aphasia, the effectiveness of conventional therapies has not been conclusively proved. This has motivated attempts to integrate knowledge from several domains in an effort to plan more rational therapies and to introduce other therapeutic strategies, including the use of intensive language therapy and pharmacological agents.Several placebo-controlled trials suggest that piracetam is effective in recovery from aphasia when started soon after the stroke, but its efficacy vanishes in patients with chronic aphasia. Drugs acting on catecholamine systems (bromocriptine, dexamfetamine) have shown varying degrees of efficacy in case series, open-label studies and placebo-controlled trials. Bromocriptine is useful in acute and chronic aphasias, but its beneficial action appears restricted to nonfluent aphasias with reduced initiation of spontaneous verbal messages. Dexamfetamine improves language function in subacute aphasia and the beneficial effect is maintained in the long term, but its use is restricted to highly selected samples.Pharmacological agents operating on the cholinergic system (e.g. donepezil) have shown promise. Data from single-case studies, case series and an open-label study suggest that donepezil may have beneficial effects on chronic poststroke aphasia. Preliminary evidence suggests that donepezil is well tolerated and its efficacy is maintained in the long term. Randomised controlled trials of donepezil and other cholinergic agents in poststroke aphasia are warranted.

Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and mixed episodes are difficult to treat and frequently require rational polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant with antikindling, inhibitory, and neuroprotective properties that is effective in an animal model of mania. This case report describes a patient with treatment-resistant rapid cycling bipolar disorder who failed 15 psychotropics, individually or in various combinations (maximum of 6), but ultimately responded to levetiracetam monotherapy and remained without bipolar features during 1 year of maintenance treatment, excluding 1 week during which the patient was medicine noncompliant. Further, methylphenidate used to treat comorbid attention deficit disorder did not precipitate manic features. Levetiracetam should be further studied for its potential use in the treatment of bipolar disorders.

BACKGROUND: Chinese herbal medicines are commonly used to improve general health and well-being despite limited scientific data to support their efficacy. We conducted a randomized, double-blind, placebo-controlled trial to determine whether an herbal remedy that is used widely in China was associated with changes in quality of life, energy, memory, sexual function, and qi (the Chinese concept of "vital energy" that is important in general health). METHODS: Residents (n = 237) of Beijing, China, who were aged > or =60 years and had self-reported decreased energy, memory, or sexual function, were randomly assigned to take four tablets of a Chinese herbal formula or of an identical placebo, three times a day for 30 days. Patients returned for one follow-up visit after 30 days for assessment of all outcomes. The main outcome measures were changes in quality of life at 30 days as measured by the 12-Item Short Form Health Survey (SF-12) Mental and Physical Component Summary scales. RESULTS: Use of Chinese herbs was associated with a small benefit in the Mental Component scale (difference of 1.9 points; 95% confidence interval [CI]: 0.1 to 3.6) and no benefit in the Physical Component scale (difference of -0.1 points; 95% CI: -1.7 to 1.5) as compared with placebo. A small improvement in the qi scale was no longer significant after adjusting for baseline differences in this score between groups. There was no improvement in physical performance, memory, or sexual function. The herbal product was well tolerated. CONCLUSION: Short-term use of a mixture of Chinese herbs was associated with a small benefit in one measure of mental health that is of unclear clinical importance.

The effect of the combined application of the alpha 2-adrenoreceptor agonist clonidine and of the dopaminergic blocker haloperidol on the memory processes was tested on albino rats. The changes in the memory were studied using the following methods: two-way active avoidance with negative reinforcement (shuttle-box) and passive avoidance (step-through). Both clonidine (0.05 mg/kg) and haloperidol (0.5 mg/kg), injected intraperitoneally immediately after the end of the training session, slightly impaired retention in the memory tests used with both training methods. Their combined application, however, caused a marked amnesia. This amnesia model was used to study the effects of the nootropic drugs: adafenoxate and the newly-synthesized compound benzoyl-1, 4-dipyrolydinone (p-P). Administered orally in a dose of 100 mg/kg for 5 days prior to the training session, both adafenoxate and p-P fully eliminate the amnesia caused by the combined application of clonidine and haloperidol. The paper discusses the role of the noradrenergic and dopaminergic neurotransmitter systems for the amnestic effect of the clonidine + haloperidol combination, as well as for the favourable effect on the cognitive functions of the tested nootropic drugs adafenoxate and p-p.

The different expressions of mental decline in elderly people, from simple senile benign forgetfulness to SDAT, can be evaluated by psychometric and neurophysiological tests. In the present study, the effects of oxiracetam, piracetam and placebo were compared in a group of elderly subjects. The results of the trial, structured as single blind, clearly showed that nootropics positively effect both clinical and neurophysiological performances and that oxiracetam produces a more pronounced effect when compared to piracetam. In fact, oxiracetam was found more effective in improving psychometric scales such as GDS (clinical performances) as well as the amplitude and the latency of the P300 (neurophysiological performances), which reflect a functional recovery of the cerebral pathways related to attention and memory.

GINKGO FAILS TO ENHANCE MEMORY IN CONTROLLED TRIAL

JAMA 2002 Aug 21;288(7):835-40
Ginkgo for memory enhancement: a randomized controlled trial
Solomon PR, Adams F, Silver A, Zimmer J, DeVeaux R
Bronfman Science Center, Williams College, 33 Hoxsey St, Williamstown, MA 01267, USA

CONTEXT: Several over-the-counter treatments are marketed as having the ability to improve memory, attention, and related cognitive functions in as little as 4 weeks. These claims, however, are generally not supported by well-controlled clinical studies.
OBJECTIVE: To evaluate whether ginkgo, an over-the-counter agent marketed as enhancing memory, improves memory in elderly adults as measured by objective neuropsychological tests and subjective ratings.
DESIGN: Six-week randomized, double-blind, placebo-controlled, parallel-group trial.
SETTING AND PARTICIPANTS: Community-dwelling volunteer men (n = 98) and women (n = 132) older than 60 years with Mini-Mental State Examination scores greater than 26 and in generally good health were recruited by a US academic center via newspaper advertisements and enrolled over a 26-month period from July 1996 to September 1998.
INTERVENTION: Participants were randomly assigned to receive ginkgo, 40 mg 3 times per day (n = 115), or matching placebo (n = 115).
MAIN OUTCOME MEASURES: Standardized neuropsychological tests of verbal and nonverbal learning and memory, attention and concentration, naming and expressive language, participant self-report on a memory questionnaire, and caregiver clinical global impression of change as completed by a companion.
RESULTS: Two hundred three participants (88%) completed the protocol. Analysis of the modified intent-to-treat population (all 219 participants returning for evaluation) indicated that there were no significant differences between treatment groups on any outcome measure. Analysis of the fully evaluable population (the 203 who complied with treatment and returned for evaluation) also indicated no significant differences for any outcome measure.
CONCLUSIONS: The results of this 6-week study indicate that ginkgo did not facilitate performance on standard neuropsychological tests of learning, memory, attention, and concentration or naming and verbal fluency in elderly adults without cognitive impairment. The ginkgo group also did not differ from the control group in terms of self-reported memory function or global rating by spouses, friends, and relatives. These data suggest that when taken following the manufacturer's instructions, ginkgo provides no measurable benefit in memory or related cognitive function to adults with healthy cognitive function.