Effects of S-adenosylmethionine augmentation of serotonin-reuptake inhibitor antidepressants on cognitive symptoms of major depressive disorder

Psychiatry Department, Shalvata Mental Health Center, Tel Aviv University, Hamargoa 4, POB 94, Tel Aviv, Israel
European Psychiatry (Impact Factor: 3.44). 06/2011; 27(7):518-21. DOI: 10.1016/j.eurpsy.2011.03.006
Source: PubMed

ABSTRACT Major depressive disorder (MDD) is often accompanied by significant cognitive impairment, and there are limited interventions specific to this particular symptom. S-adenosylmethionine (SAMe), a naturally occurring molecule which serves as a major methyl-donor in human cellular metabolism, is required for the synthesis and maintenance of several neurotransmitters that have been implicated in the pathophysiology and treatment of cognitive dysfunction in MDD.
This study is a secondary analysis of a clinical trial involving the use of adjunctive SAMe for MDD.
Forty-six serotonin-reuptake inhibitor (SRI) non-responders with MDD enrolled in a 6-week, double-blind, randomized trial of adjunctive oral SAMe were administered the self-rated cognitive and physical symptoms questionnaire (CPFQ), a validated measure of cognitive as well as physical symptoms of MDD, before and after treatment.
There was a greater improvement in the ability to recall information (P=0.04) and a trend towards statistical significance for greater improvement in word-finding (P=0.09) for patients who received adjunctive SAMe than placebo. None of the remaining five items reached statistical significance.
These preliminary data suggest that SAMe can improve memory-related cognitive symptoms in depressed patients, and warrant replication.

3 Reads
  • Source
    • "Another compound currently under investigation for its pro-cognitive potential is S-adenosyl methionine (SAMe), a major methyl-donor required for the synthesis of several neurotransmitters. Preliminary encouraging results have been provided by a randomized, double-blind, placebo-controlled 6 week trial on 40 SSRI-resistant outpatients with MDD [156]. Participants allocated to SAMe therapy showed significant improvements in recall and word-finding scores on the self-rated Cognitive and Physical Symptoms Questionnaire (CPFQ) compared to placebo. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Major depressive disorder (MDD) is a prevalent and recurring mental disorder often associated with high rates of non-recovery and substantial consequences on psychosocial outcome. Cognitive impairment is one of the most frequent residual symptoms of MDD. The persistence of cognitive impairment even in remitted phases of the disorder, notably in the domains of executive function and attention, suggests that it may serve as a mediational nexus between MDD and poor functional outcome, accounting for occupational and relational difficulties regardless of clinical improvement on depressive symptoms. The critical impact of cognitive deficits on psychosocial dysfunction invites clinicians to regularly screen and assess cognition across multiple domains, taking into account also clinical correlates of cognitive dysfunction in MDD. Despite the availability of several instruments for the screening and assessment of cognitive dysfunction, the lack of consensus guiding the choice of appropriate instruments increases the likelihood to underestimate cognitive dysfunction in MDD in clinical settings. On the other hand, the unsatisfactory effect of most antidepressant treatments on cognitive deficits for many individuals with MDD calls for the development of genuinely novel therapeutic agents with potential to target cognitive dysfunction. Notwithstanding the necessity of further investigations, this review indicates that neuropsychological deficits (e.g., impaired executive functions) are stable markers of MDD and underscores the need for the development of integrative and multi-modal strategies for the prevention and treatment of neuropsychological impairments in MDD.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 11/2014; 13(10). DOI:10.2174/1871527313666141130203823 · 2.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this trial was to assess the feasibility and safety of using S-adenosyl-L-methionine (SAMe) to treat depressive disorder, attention deficit/hyperactivity disorder (ADHD) and cognitive deficits in individuals with the 22q11.2 deletion syndrome (22q11.2DS). SAMe supposedly enhances the activity of the COMT enzyme. Because individuals with 22q11.2DS have only one copy of the gene responsible for the enzyme, COMT haploinsufficiency may be associated with their psychiatric morbidity and cognitive deficits. We assessed twelve 22q11.2DS individuals with depressive disorder or ADHD in a randomized double-blind cross-over placebo-controlled trial, using SAMe 800 mg bid. Individuals were evaluated for treatment safety and effectiveness during the trial and upon completion at sixth week. Compared to placebo, there were no significant differences in the rate of reported side effects between SAMe and placebo. Despite a general concern that SAMe might induce mania in vulnerable individuals, no manic or psychotic symptoms were exhibited during the SAMe treatment. Individuals with 22q11.2DS with comorbid depressive disorder with or without psychotic symptoms (n = 5) had a larger numerical improvement on relevant clinical scales compared to placebo. No treatment effect was found on ADHD symptoms in subjects who suffered from 22q11.2DS with comorbid ADHD (n = 7). Cognitive performance did not improve or deteriorate following treatment with SAMe compared to placebo. In conclusion SAMe treatment up to 1,600 mg/day for 6 weeks in 22q11.2DS individuals appears to be safe, well tolerated and with no serious side effects. No significant benefit in depressive or ADHD symptoms was detected.
    Journal of Neural Transmission 06/2012; 119(11):1417-23. DOI:10.1007/s00702-012-0831-x · 2.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Complementary and alternative medicine therapies are increasingly sought out by people with psychiatric disorders. In this chapter, we review the evidence for several commonly used CAM therapies (i.e. omega-3 fatty acids, folate, S-adenosyl-methionine, St John's Wort, bright light therapy, exercise, massage, and acupuncture) in the treatment of perinatal depression. A number of these treatments may be reasonable to consider for women during pregnancy or postpartum, but the safety and efficacy of these relative to standard treatments must still be systematically determined. Evidence-based use of complementary and alternative medicine therapies treatments for perinatal depression is discussed. Adequately powered systematic studies are necessary to determine the role of complementary and alternative medicine therapies in the treatment of perinatal depression.
    Best practice & research. Clinical obstetrics & gynaecology 08/2013; 28(1). DOI:10.1016/j.bpobgyn.2013.08.007 · 1.92 Impact Factor
Show more