St. John's wort for treating depression. Cochrane Review

Authors’ conclusions

The available evidence suggests that the hypericum extracts tested in the included trials a) are superior to placebo in patients with major depression; b) are similarly effective as standard antidepressants; c) and have fewer side effects than standard antidepressants. The association of country of origin and precision with effects sizes complicates the interpretation.

Commentary: It should be noted that the comparator dosages for standard anti-depressant medications were in the lower dosage ranges.

SJW Dosages used in comparator studies: 240-1800 mg (500-1200 mg most common dosage range)

Fluoxetine (SSRI) Prozac 
20-40 mg
6 trials
Sertraline (SSRI) Zoloft
50-100 mg
4 trials
Citalopram (SSR) Celexa
20 mg
1 trial
Paroxetine (SSRI) Paxel
20-40 mg
1 trial
Maprotiline (TeCA) Deprilept
75 mg* Dosage slightly below those recommended
1 trial
Imipramine (TCA) Tofranil
100-150 mg
3 trials
Amitriptyline (TCA) Elavil
75 mg* Dosage slightly below those recommended
1 trial



Tryptophan and 5-Hydroxytryptophan for depression Cochrane Review

A large number of studies appear to address the research questions, but few are of sufficient quality to be reliable. Available evidence does suggest these substances are better than placebo at alleviating depression. Further studies are needed to evaluate the efficacy and safety of 5-HTP and tryptophan before their widespread use can be recommended. The possible association between these substances and the potentially fatal Eosinophilia-Myalgia Syndrome has not been elucidated. Because alternative antidepressants exist which have been proven to be effective and safe the clinical usefulness of 5-HTP and tryptophan is limited at present.


An epidemic of EMS in 1989 was linked to L-tryptophan consumption originating from a single contaminated source, resulting in 150o individuals being affected with 30 deaths. The EMS outbreak was traced to the presence of an impurities in the L-tryptophan produced by Showa Denko K.K., a Japanese wholesaler that was the major supplier to American manufacturers. Since the FDA ban on L-tryptophan was lifted in 2005 there have been no documented cases of EMS in connection with L-tryptophan consumption.

It should also be noted that the statement that antidepressants are safe in comparison to L-tryptophan and 5-HTP and therefore a better alternative is grossly misleading.  Antidepressants carry many well documented side effects including an increased risk of suicide in certain age groups.

Folate for depression. Cochrane Review

This systematic review was undertaken to see if giving folate to people with depressive disorders reduced their depressive symptoms. Three randomized trials were identified, involving a total of 247 people. In all three trials, folate was well tolerated. In two of these trials, folate was added to other antidepressant drug treatment and there was limited evidence that folate helped. In the third trial, folate was compared to trazodone, an antidepressant drug. No difference was found. There is therefore limited evidence that adding folate to other antidepressant may be helpful, but larger trials are needed before patients and clinicians can be confident that it will be helpful. The limited available evidence suggests folate may have a potential role as a supplement to other treatment for depression. It is currently unclear if this is the case both for people with normal folate levels, and for those with folate deficiency.


Inositol for depression. Cochrane Review

There are a number of effective interventions for the treatment of depression. It is possible that the efficacy of these treatments will be improved further by the use of adjunctive therapies such as inositol.” “Inositol is a nutritional supplement that has been suggested as a treatment for depressive disorders. The reviewers found the current evidence is unclear whether or not inositol is of benefit in the treatment of depression. There are ongoing studies that should reduce this uncertainty.”


Omega-3 fatty acids for depression in adults. Cochrane Review

Authors’ conclusions

At present, we do not have sufficient high quality evidence to determine the effects of n-3PUFAs as a treatment for MDD. Our primary analyses suggest a small-to-modest, non-clinically beneficial effect of n-3PUFAs on depressive symptomology compared to placebo; however the estimate is imprecise, and we judged the quality of the evidence on which this result is based to be low/very low. Sensitivity analyses, funnel plot inspection and comparison of our results with those of large well-conducted trials also suggest that this effect estimate is likely to be biased towards a positive finding for n-3PUFAs, and that the true effect is likely to be smaller. Our data, however, also suggest similar rates of adverse events and numbers failing to complete trials in n-3PUFA and placebo groups, but again our estimates are very imprecise. The one study that directly compares n-3PUFAs and antidepressants in our review finds comparable benefit. More evidence, and more complete evidence, are required, particularly regarding both the potential positive and negative effects of n-3PUFAs for MDD.




FDA Warning: Questions and Answers on Antidepressant Use in Children, Adolescents, and Adults: May, 2007

What is FDA announcing regarding the use of antidepressants? 

FDA is announcing a request to manufacturers of all antidepressant medications to update the existing “black box” on their product labeling to include warnings about increased risks of suicidal thinking and behavior (suicidality) in young adults ages 18 to 24 during initial treatment.

The labeling also will point out that scientific data did not show this increased risk in adults older than 24 and that adults ages 65 and older taking antidepressants actually have a decreased risk of suicidality. The warning statements will emphasize that depression and certain other serious psychiatric disorders are themselves the most important causes of suicide.

Drug manufacturers will have 30 days to submit their revised labeling and revised Patient Medication Guides to the FDA for review.  Medication Guides are FDA-approved user-friendly information for patients, families and caregivers that could help improve monitoring. Medication Guides are intended to be distributed at the pharmacy with each prescription or refill of a medication.

Why is FDA making this announcement now? 

In December 2006, the FDA’s Psychopharmacologic Drugs Advisory Committee agreed that labeling changes were needed to inform health care professionals about the increased risk of suicidality in younger adults using antidepressants.  Additionally, the committee recommended that product labeling note that no increased risk of suicidality was seen in adults older than 24 and that adults ages 65 and older taking antidepressants actually had a decreased risk of suicidality. Finally, the committee recommended that labeling remind health care professionals that depression and other disorders being treated with these drugs are serious illnesses that need to be recognized and effectively treated.

What products are involved in this announcement of a labeling change? 

The requested labeling changes apply to the entire category of antidepressants. Products involved in today’s action include: Anafranil (clomipramine), Asendin (amoxapine), Aventyl (nortriptyline), Celexa (citalopram hydrobromide), Cymbalta (duloxetine), Desyrel (trazodone HCl), Elavil (amitriptyline), Effexor (venlafaxine HCl), Emsam (selegiline), Etrafon (perphenazine/amitriptyline), fluvoxamine maleate, Lexapro (escitalopram hydrobromide), Limbitrol (chlordiazepoxide/amitriptyline), Ludiomil (maprotiline), Marplan (isocarboxazid), Nardil (phenelzine sulfate), nefazodone HCl, Norpramin (desipramine HCl), Pamelor (nortriptyline), Parnate (tranylcypromine sulfate), Paxil (paroxetine HCl), Pexeva (paroxetine mesylate), Prozac (fluoxetine HCl), Remeron (mirtazapine), Sarafem (fluoxetine HCl), Seroquel (quetiapine), Sinequan (doxepin), Surmontil (trimipramine), Symbyax (olanzapine/fluoxetine), Tofranil (imipramine), Tofranil-PM (imipramine pamoate), Triavil (perphenazine/amitriptyline), Vivactil (protriptyline), Wellbutrin (bupropion HCl), Zoloft (sertraline HCl), and Zyban (bupropion HCl).

Are the drugs mentioned above approved for use in children and adolescents? 

Prozac (fluoxetine) is approved for use in children and adolescents for the treatment of major depressive disorder. Prozac (fluoxetine), Zoloft (sertraline), and fluvoxamine maleate are approved for use in children and adolescents for the treatment of obsessive compulsive disorder. The other drugs have no approved uses in children.

I am currently taking an antidepressant. What should I do? 

If you observe worsening depression, or the emergence of suicidal thinking, or if you are experiencing other symptoms that you are concerned might be related to taking your medication, you should consult your doctor to discuss the best course of action.  It is very important that you do not stop taking your antidepressant without first checking with your doctor. Also, some of these medications may be associated with discontinuation symptoms if stopped abruptly. If your doctor advises that your medication should be stopped, be sure to follow your doctor’s advice about how to accomplish this.

My child or adolescent, or someone else I am caring for, is currently taking an antidepressant. What should I do? 

If you observe worsening depression, or the emergence of suicidal thinking, or if you observe other symptoms that you are concerned might be related to taking medication, you should consult the doctor responsible for your child’s or this person’s medications to discuss the best course of action. It is very important that you do not stop your child’s or this person’s antidepressant without first checking with the prescribing doctor. Alsosome of these medications may be associated with discontinuation symptoms if stopped abruptly, so that, if the doctor advises that the medication should be stopped, be sure to follow the doctor’s advice about how to accomplish this.


Antidepressants compared with placebos for depressed older people. Cochrane Review

TCAs, SSRIs and MAOIs are effective in the treatment of older community patients and inpatients likely to have severe physical illness. At least six weeks of antidepressant treatment is recommended to achieve optimal therapeutic effect. There is little evidence concerning the efficacy of low dose TCA treatment. Further trials are required before low dose TCA treatment is routinely recommended.









Tricyclic Antidepressants

Tricyclic antidepressants compared with active placebos for depression. Cochrane Review

This review examined trials which compared antidepressants with ‘active’ placebos, that is placebos containing active substances which mimic side effects of antidepressants. Small differences were found in favour of antidepressants in terms of improvements in mood. This suggests that the effects of antidepressants may generally be overestimated and their placebo effects may be underestimated. The more conservative estimates from the present analysis found that differences between antidepressants and active placebos were small. This suggests that unblinding effects may inflate the efficacy of antidepressants in trials using inert placebos. Further research into unblinding is warranted.

SSRIs (Selective Serotonin Reuptake Inhibitors)

Fluoxetine (Prozac) compared with other antidepressants for depression in adults. Cochrane Review

The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain. Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies’ results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful, as already suggested by other systematic reviews. In addition to efficacy data, treatment decisions should also be based on considerations of drug toxicity, patient acceptability and cost.











Acupuncture for depression Cochrane Review

Authors’ conclusions We found insufficient evidence to recommend the use of acupuncture for people with depression. The results are limited by the high risk of bias in the majority of trials meeting inclusion criteria.






Is dance movement therapy an effective treatment for depression? A review of the evidence Cochrane Review

Authors’ conclusions: The low-quality evidence from three small trials with 147 participants does not allow any firm conclusions to be drawn regarding the effectiveness of DMT for depression. Larger trials of high methodological quality are needed to assess DMT for depression, with economic analyses and acceptability measures and for all age groups.






Family therapy for depression Cochrane Review

Authors’ conclusions: The current evidence base is too heterogeneous and sparse to draw conclusions on the overall effectiveness of family therapy in the treatment of depression. At this point, use of psychological interventions for the treatment of depression for which there is already an evidence-base would seem to be preferable to family therapy. Further high quality trials examining the effectiveness and comparative effectiveness of explicitly defined forms of family therapy are required.






Exercise for depression Cochrane Review

Authors’ conclusions: Exercise is moderately more effective than a control intervention for reducing symptoms of depression, but analysis of methodologically robust trials only shows a smaller effect in favour of exercise. When compared to psychological or pharmacological therapies, exercise appears to be no more effective, though this conclusion is based on a few small trials.






Music therapy for depression Cochrane Review

Authors’ conclusions: Findings from individual randomised trials suggest that music therapy is accepted by people with depression and is associated with improvements in mood. However, the small number and low methodological quality of studies mean that it is not possible to be confident about its effectiveness. High quality trials evaluating the effects of music therapy on depression are required.






Reiki for the treatment of anxiety and depression Cochrane Review

Authors’ conclusions: There is insufficient evidence to say whether or not Reiki is useful for people over 16 years of age with anxiety or depression or both.






Relaxation for depression Cochrane Review

Authors’ conclusions: Relaxation techniques were more effective at reducing self-rated depressive symptoms than no or minimal treatment. However, they were not as effective as psychological treatment. Data on clinician-rated depressive symptoms were less conclusive. Further research is required to investigate the possibility of relaxation being used as a first-line treatment in a stepped care approach to managing depression, especially in younger populations and populations with subthreshold or first episodes of depression.






Transcranial magnetic stimulation (TMS) for depression Cochrane Review

Authors’ conclusions: The information in this review suggests that there is no strong evidence for benefit from using transcranial magnetic stimulation to treat depression, although the small sample sizes do not exclude the possibility of benefit.