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Phenothiazine drugs are primarily used for the treatment of schizophrenia and other forms of psychosis.

Medications in this family include

  • Chlorpromazine hydrochloride (Thorazine)
  • Fluphenazine (Permitil, Prolixin)
  • Mesoridazine besylate (Serentil)
  • Perphenazine (Trilafon)
  • Prochlorperazine (Compazine)
  • Promazine hydrochloride (Sparine)
  • Promethazine hydrochloride (Anergan [injectable], Phenergan)
  • Thioridazine hydrochloride (Mellaril)
  • Trifluoperazine hydrochloride (Stelazine)
  • Triflupromazine hydrochloride (Vesprin [injectable])
  • and others


Substance: Coenzyme Q 10 (CoQ 10 )

Effect: Supplementation Possibly Helpful

Preliminary studies suggest that phenothiazine drugs might deplete the body of coenzyme Q 10 (CoQ 10).1,2 While there is as yet no evidence that taking CoQ 10 supplements provides any specific benefit, supplementing with CoQ 10 on general principle might be a good idea if you are taking phenothiazine drugs.


Substance: Fish Oil

Effect: Possible Helpful Interaction

Fish oil contains essential fatty acids in the omega-3 family. Fish oil, its constituents, and a slightly modified fish oil constituent called ethyl-EPA have all been tested for treatment of depression. Incomplete and inconsistent evidence hints that these substances might augment the effectiveness of standard medications used for schizophrenia.15-20


Substance: Milk Thistle

Effect: Possible Helpful Interaction

Milk thistle might protect against the liver toxicity sometimes caused by phenothiazine drugs.3


Substance: Ginkgo

Effect: Possible Helpful Interaction

Preliminary evidence suggests that ginkgo might reduce the side effects and increase the efficacy of various antipsychotic medications.4,12


Substance: Vitamin E

Effect: Possible Helpful Interaction

One of the most feared side effects of phenothiazines is the development of a permanent side effect called tardive dyskinesia (TD). This late-developing (tardy, or tardive) complication consists of annoying uncontrollable movements (dyskinesias), particularly in the face.

In early studies, vitamin E had shown some promise for treating tardive dyskinesia,5,6 but the largest and best-designed study failed to find benefit.21 For more information, see the full Tardive Dyskinesia article.


Substance: Vitamin B 6

Effect: Possible Helpful Interaction

A pilot study suggests that vitamin B 6 may be helpful for the treatment of tardive dyskinesia (TD). In this 4-week, double-blind crossover trial of 15 individuals, treatment with vitamin B 6 significantly improved TD symptoms as compared to placebo.11 Benefits were seen after 1 week of treatment. However, the dosage of vitamin B 6 used in this study was quite high (400 mg daily). Toxicity has been reported with daily intake of vitamin B 6 at half this dose.

Vitamin B 6 might also reduce symptoms of akathesia, a type of restlessness associated with phenothiazine antipsychotics.13


Substance: Dehydroepiandrosterone (DHEA)

Effect: Possible Helpful Interaction

One small, double-blind study found that use of DHEA reduced the Parkinson-like movement disorders that may occur in people taking phenothiazine drugs.14


Substance: Glycine

Effect: Possible Helpful Interaction

Phenothiazine drugs are most effective for the "positive" symptoms of schizophrenia, such as hallucinations and delusions. (Such symptoms are called "positive" because they indicate the presence of abnormal mental functions, rather than the absence of normal mental functions.) In general, however, these medications are less helpful for the "negative" symptoms of schizophrenia, such as apathy, depression, and social withdrawal. Some evidence hints that the supplement glycine might enhance the effectiveness of phenothiazines regarding this latter class of symptoms.22-24


Substance: Phenylalanine

Effect: Possible Increased Risk of Tardive Dyskinesia

There are some indications that using the supplement phenylalanine while taking antipsychotic drugs might increase your risk of developing tardive dyskinesia.7,8


Substance: Kava

Effect: Possible Increased Risk of Dystonic Reactions

Besides the late-developing complication of tardive dyskinesia, antipsychotic drugs can cause more immediately another movement disorder: dystonic reactions, sudden intense movements of the neck and eyes. There is some evidence that the herb kava can increase the risk or severity of this side effect.9


Substance: St. John's Wort , Other Herbs

Effect: Potential Increased Risk of Photosensitivity

Phenothiazines can cause increased sensitivity to the sun. Various herbs, including St. John's wort and dong quai, can also cause this problem. Combined treatment with herb and drug might increase the risk further.


Substance: Yohimbe

Effect: Possible Dangerous Interaction

The herb yohimbe is relatively toxic, and can cause problems if used incorrectly. Phenothiazine medications may increase the risk of toxicity.10



1. Folkers K. Basic chemical research on coenzyme Q 10 and integrated clinical research on therapy of diseases. In Lenaz G, ed. Coenzyme Q. New York: John Wiley and Sons, 1985.

2. Kishi T, Makino K, Okamoto T, et al. Inhibition of myocardial respiration by psychotherapeutic drugs and prevention by coenzyme Q. In: International Symposium on Coenzyme Q. Biomedical and clinical aspects of coenzyme Q. Vol 2. New York, NY: Elsevier Science Publishing Co; 1980: 139-157.

3. Palasciano G, et al. The effect of silymarin on plasma levels of malondialdehyde in patients receiving long term treatment with psychotropic drugs. Curr Ther Res 1994;55:537-545, 1994.

4. Liu P, et al. Combined use of Ginkgo biloba extracts on efficacy and adverse reactions of various antipsychotics. Zhongguo Linchuang Yaolixue Zaxhi. 1997;13:193-198.

5. Adler LA, et al. Vitamin E treatment of tardive dyskinesia. Am J Psychiatry. 1993;50:1405-1407.

6. Adler LA, et al. Long term treatment effects of vitamin E for tardive dyskinesia. Biol Psychiatry. 1998;43:868-872.

7. Richardson MA. Amino acids in psychiatric disease. Washington, DC: American Psychiatric Press; 1990.

8. Mosnik DM, Spring B, Rogers K, and Baruah SL. Tardive dyskinesia exacerbated after ingestion of phenylalanine by schizophrenic patients. Neuropsychopharmacology 1997;16:136-146.

9. Schelosky L, et al. Kava and dopamine antagonism. J Neurol Neurosurg Psych 1995;58:639-640.

10. Brinker F. Herb contraindications and drug interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications. 1998: 140-141.

11. Lerner V, Miodownik C, Kaptsan A, et al. Vitamin B 6 in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study. Am J Psychiatry. 2001;158:1511-1514.

12. Zhang XY, Zhou DF, Zhang PY, et al. A double-blind, placebo-controlled trial of extract of Ginkgo biloba added to haloperidol in treatment-resistant patients with schizophrenia. J Clin Psychiatry. 2001;62:878-883

13. Lerner V, Bergman J, Statsenko N, et al. Vitamin B(6) treatment in acute neuroleptic-induced akathisia: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2004;65:1550-1554.

14. Nachshoni T, Ebert T, Abramovitch Y, et al. Improvement of extrapyramidal symptoms following dehydroepiandrosterone (DHEA) administration in antipsychotic treated schizophrenia patients: A randomized, double-blind placebo controlled trial. Schizophr Res. 2005 Aug 25. [Epub ahead of print]

15. Berger GE, Proffitt TM, McConchie M, et al. Ethyl-eicosapentaenoic acid in first-episode psychosis: a randomized, placebo-controlled trial. J Clin Psychiatry. 2007;68:1867-1875.

16. Peet M, Brind J, Ramchand CN, et al. Two double-blind placebo-controlled pilot studies of eicosapentaenoic acid in the treatment of schizophrenia. Schizophr Res. 2001;49:243-251.

17. Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001;158:2071-2074.

18. Emsley R, Myburgh C, Oosthuizen P, et al. Randomized, placebo-controlled study of ethyl-eicosapentaenoic Acid as supplemental treatment in schizophrenia. Am J Psychiatry. 2002;159:1596-1598.

19. Fenton WS, Dickerson F, Boronow J, et al. A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia. Am J Psychiatry. 2001;158:2071-2074.

20. Peet M. Eicosapentaenoic acid in the treatment of schizophrenia and depression: rationale and preliminary double-blind clinical trial results. Prostaglandins Leukot Essent Fatty Acids. 2003;69:477-485.

21. Adler LA, Rotrosen J, Edson R, et al. Vitamin E treatment for tardive dyskinesia. Arch Gen Psychiatry. 1999;56:836-841.

22. Heresco-Levy U, Javitt DC, Ermilov M, et al. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999;56:29-36.

23. Heresco-Levy U, Javitt DC, Ermilov M, et al. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br J Psychiatry. 1996;169:610-617.

24. Javitt DC, Zylberman I, Zukin SR, et al. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry. 1994;151:1234-1236.

Last reviewed December 2015 by EBSCO CAM Review Board