Tryptophan and 5-Hydroxytryptophan for depression

  • Review
  • Intervention




5 Hydroxytryptophan (5-HTP) and tryptophan are so-called natural alternatives to traditional antidepressants, used to treat unipolar depression and dysthymia.


To determine whether 5-HTP and tryptophan are more effective than placebo, and whether they are safe to use to treat depressive disorders in adults.

Search methods

CCDANCTR-Studies and CCDANCTR-References were searched on 12/2/2008). Reference lists, book chapters and conference proceedings were checked. Experts and trialists were contacted for unpublished studies.

Selection criteria

Trials were included if they were randomized, included patients with unipolar depression or dysthymia, compared preparations of 5-HTP or tryptophan with placebo, and included clinical outcomes assessed by scales assessing depressive symptoms.

Data collection and analysis

Data was extracted independently by the three reviewers, onto data collection forms. Inclusion criteria were applied to all potential studies independently and a coefficient of agreement (Kappa) was calculated for them. Disagreement was resolved by reaching consensus. Trial quality was scored according to risk of bias. Analysis for 5-HTP and tryptophan were combined due to the small number of included trials.

Main results

108 trials were located using the specified search strategy in 2001. An additional three trials were located when the search strategy was repeated in 2004. Of the total number of trials located in both searches, only two trials, involving a total of 64 patients, were of sufficient quality to meet inclusion criteria. The available evidence suggests these substances were better than placebo at alleviating depression (Peto Odds Ratio 4.10; 95% confidence interval 1.28-13.15; RD 0.36; NNT 2.78). However, the evidence was of insufficient quality to be conclusive.

Authors' conclusions

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.



Tryptophan and 5Hydroxytryptophan在憂鬱的應用

5 Hydroxytryptophan (5HTP)及tryptophan被稱作傳統抗憂鬱劑的天然替代物,可用來治療單極性憂鬱症及輕鬱症.




CCDANCTR以下列搜尋策略(Diagnosis = Depress∗ or Dysthymi∗ and Intervention = tryptophan or 5htp or 5hydroxtryptophan or Hydroxytryptophan and Intervention = Placebo). 來搜尋試驗(於2005年12月1日完成). 另外,也包括參考文獻列表,書籍章節及進行中之研討會. 我們也聯繫專家及試驗作者關於未發表試驗.




數據由3位回顧者獨立解讀為資料收集格式. 納入規則獨立應用在所有重要性的研究並計算一致性係數(Kappa). 不一致的狀況藉由取得共識來解決. 根據偏誤的危險性來評比試驗品質. 針對5HTP及tryptophan的分析因為試驗數太少太小而被合併評估.


在2001年,我們使用特定搜尋策略找出108篇試驗. 額外的3篇研究在2004年的重新搜尋中被搜尋到. 兩次搜尋中的所有試驗,其中只有包含64位病患的兩個試驗能夠適切地符合納入規則. 目前可獲得的證據顯示這些物質較安慰劑能夠緩解憂鬱(Peto Odds Ratio 4.10; 95% confidence interval 1.28 – 13.15; RD 0.36; NNT 2.78). 然而,卻未有適當品質去確立決定性的證據.


大量的研究看起來能呈現研究問題,但只有少數是有品質而可信賴的. 目前可獲得的證據顯示這些物質較安慰劑能夠緩解憂鬱. 在5HTP及tryptophan被廣泛建議使用前,需要進一步的研究來評估它們的效果與安全性. 這些物質和致命的嗜伊紅性肌痛症侯群(Eosinophilia myalgia syndrome)之間的關連性並不明確. 目前替代的抗憂鬱劑在臨床使用上被證明有療效及安全,因而限制了5HTP and tryptophan 的使用.



此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。


5HTP (Hydroxytryptophan)與tryptophan 已經被檢驗在成人單極性憂鬱症是否是有效,安全即可接受的. 研究者報告5HTP與tryptophan對比安慰劑(非藥物)可減少憂鬱症狀. 然而,會有副作用出現(頭暈,噁心及腹瀉). 它們也報告tryptophan和致命狀況的發展相關. 在強大及有意義的結論產生前仍需要更多證據來評估效果及安全性. 直到目前,回顧者提出抗憂鬱劑因未有致命的副作用而更吸引人. 此回顧研究提出在方法學上,我們仍需有效地研究在合適的對照試驗裡這些物質的效用.

Plain language summary

Tryptophan and 5-Hydroxytryptophan for depression

5-HTP (Hydroxytryptophan) and tryptophan have been examined to see whether these treatments are effective, safe and acceptable in treating unipolar depression in adults. The researchers reported that the symptoms of depression decreased when 5-HTP and tryptophan were compared to a placebo (non-drug). However, side effects had occurred (dizziness, nausea and diarrhoea). They also reported that tryptophan has been associated with the development of a fatal condition. More evidence is needed to assess efficacy and safety, before any strong and meaningful conclusions can be made. Until then, the reviewers propose that the use of antidepressants which have no known life threatening side effects remain more attractive. The review sets out the required methodology for effectively studying these substances in proper controlled studies.