Skip to main content

Diutensen-R Side Effects

Generic name: methyclothiazide / reserpine

Note: This document contains side effect information about methyclothiazide / reserpine. Some dosage forms listed on this page may not apply to the brand name Diutensen-R.

Applies to methyclothiazide/reserpine: oral tablet.


Respiratory side effects including nasal congestion has been reported in 8% of patients receiving reserpine. Bronchospasm is a rare respiratory system side effect associated with reserpine.[Ref]

Rare reports of reserpine-induced bronchospasm are believed to be due to inactivation of beta-adrenergic receptors, which can result in a marked potentiation of the bronchoconstrictive effect of histamine.[Ref]

Nervous system

Nervous system side effects associated with reserpine include sedation, lethargy (different from the psychiatric syndrome of depression), drowsiness, weakness, vertigo, insomnia, or headache in approximately 1% to 5% of patients. Vertigo, paresthesias, and restlessness have been associated with the use of methyclothiazide. While reserpine has been used to treat tardive dyskinesia, extrapyramidal movements may worsen upon withdrawal of therapy. A case of CNS hypertension, believed to be due to cerebral edema, has been associated with reserpine.[Ref]

Increased parkinsonian movements upon reserpine withdrawal (as with neuroleptics) may be due to supersensitivity to dopamine as a result of increased dopamine receptors that developed during reserpine therapy.[Ref]


The depressive syndrome associated with reserpine usually consists of melancholy, loss of self confidence, early morning awakening, loss of libido, and reduced appetite.

A case of reserpine withdrawal psychosis has been reported. This uncommon condition may be due to dopamine receptor supersensitivity, which develops during reserpine therapy.[Ref]

Psychiatric problems related to reserpine therapy can be serious. Depression occurs in 2% to 28% of patients, is more likely when daily doses exceed 0.5 mg, and can present at any time during therapy. Suicidal ideation has been reported. Reserpine-induced depression is quickly reversible if therapy is withdrawn as soon as the syndrome is recognized, but can persist for several months after drug discontinuation if the syndrome fully develops. Reserpine withdrawal psychosis has been reported.[Ref]


Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.[Ref]

Metabolic changes associated with methyclothiazide, as with other thiazide diuretics, are relatively common, especially when daily doses greater than 5 mg are used. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50%, and may predispose patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypophosphatemia, hypercalcemia, hyperglycemia, hypercholesterolemia, and hyperuricemia are also relatively common. The electrolyte and intravascular fluid shifts that may occur during methyclothiazide diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis.[Ref]


Orthostatic hypotension associated with methyclothiazide may be potentiated by concomitant use of alcohol, barbiturates, or narcotics.

A woman with paroxysmal atrial tachycardia developed sinus pauses during reserpine therapy, which were reproducible by carotid massage except when isoproterenol was given. Reserpine is known to increase vagal tone and to deplete cardiac catecholamines.

One patient, in a series of 231, with emergent hypertension, stroke, and thyrotoxic crisis, developed profound hypotension after reserpine 1 mg IM. Her blood pressure dropped from 180/100 to an unmeasurable level. The patient recovered after isoproterenol therapy.[Ref]

Cardiovascular side effects associated with reserpine include hypotension in 8% and bradycardia (and rare cases of syncope with bradycardia) in 3% of patients. Orthostatic hypotension secondary to intravascular volume depletion may occur during methyclothiazide therapy. This has resulted in syncope and, in some patients with glaucoma, temporary loss of vision. A rare case of paroxysmal atrial tachycardia with block associated with reserpine in a patient who was not raking a digitalis preparation, and rare cases of cerebrovascular accident associated with thiazide-induced diuresis have been reported.[Ref]


Hypersensitivity reactions to thiazides usually involve the skin (cutaneous vasculitis, urticaria, rash, purpura), but may involve the gastrointestinal system (nausea, vomiting, or diarrhea), the genitourinary system (interstitial nephritis), and the respiratory system (acute noncardiogenic pulmonary edema, pneumonitis). Thiazide diuretics may induce phototoxic dermatitis.[Ref]

Thiazides may induce allergic reactions in patients who are allergic to sulfonamides.[Ref]


Dermatologic reactions may indicate hypersensitivity to methyclothiazide. Erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia have been associated with this drug or other thiazides in rare cases.[Ref]


A retrospective case-controlled drug surveillance study has revealed the relative risk of acute cholecystitis associated with the use of a thiazide diuretic is 2.0. The suspected explanation for this association is the potentially deleterious effects of thiazides on the serum lipid profile. Methyclothiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]

Gastrointestinal side effects due to unopposed parasympathetic activity produced by catecholamine depletion may occur as a result of increased gastrointestinal motility and secretory activity. Because of this, new diarrhea or worsening of existing diarrhea or increased salivation are reported in 2% of patients. Increased appetite, abdominal pain, or vomiting are rarely associated with reserpine. More common gastrointestinal problems associated with methyclothiazide include diarrhea, vomiting, constipation, or abdominal pain in approximately 5% of patients. Thiazide diuretics have been associated with acute cholecystitis and rare cases of pancreatitis, sialadenitis, and anorexia.[Ref]


Renal side effects including new or worsened renal insufficiency associated with methyclothiazide therapy is a probably sign of intravascular volume depletion, and serves a signal to reduce or withhold therapy. Rare cases of allergic interstitial nephritis have been associated with some thiazide diuretics.[Ref]


Genitourinary complaints are limited to sexual impotence, reported in up to 5% of male patients who are taking either reserpine or methyclothiazide.[Ref]


Endocrinologic changes associated with methyclothiazide, as with other thiazide diuretic agents, include decreased glucose tolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease. Reserpine may induce hyperprolactinemia, which can result in gynecomastia in men, and breast engorgement or pseudolactation in women.[Ref]


Hematologic side effects are rare. Rare cases of immune-complex hemolytic anemia, aplastic anemia, leukopenia, and thrombocytopenia have been associated with methyclothiazide or other thiazide diuretics.[Ref]


Musculoskeletal cramping or spasms are occasionally reported during thiazide diuresis.[Ref]


Immunologic side effects are rare. A single case of angioimmunoblastic lymphadenopathy has been associated with reserpine. In one study of 231 patients who were taking reserpine, only one case of a lupus-like syndrome was observed in a patient who had previously received hydralazine.[Ref]

A 79-year-old woman with hypertension, taking reserpine, potassium, hydrochlorothiazide, and ibuprofen, developed fatigue, anorexia, fever, night sweats, and weight loss. Associated laboratory findings showed anemia, lymphocytosis, thrombocytopenia, IgA kappa paraproteinemia, an elevated ANA titer, and a positive Coombs' test. Bone marrow biopsy, lymphangiography, and lymph node biopsy showed bone marrow lymphocytosis, enlarged foamy abdominal lymph nodes with irregular filling, and angioimmunoblastic lymphadenopathy, respectively. Within four days after discontinuation of reserpine (her other medications were continued), the paraprotein level normalized and the platelet count rose. After an additional nine months of prednisone therapy, all signs and symptoms resolved.[Ref]


Oncologic concerns were raised after a large drug surveillance center in Boston reported an association between reserpine, a stimulator of prolactin, and breast cancer in 1974. This association was partially, but not completely, confirmed in two similar centers in Europe. A critical review of these studies elucidated several design flaws. Subsequent, controlled studies failed to show an association between reserpine and an increased incidence of breast carcinoma.[Ref]


1. Freis ED. Reserpine in hypertension: present status. Am Fam Physician. 1975;11:120-2.

2. Luxenberg J, Feigenbaum LZ. The use of reserpine for elderly hypertensive patients. J Am Geriatr Soc. 1983;31:556-9.

3. Applegate WB, Carper ER, Kahn SE, Westbrook L, Linton M, Baker MG, Runyan JW, Jr. Comparison of the use of reserpine versus alpha-methyldopa for second step treatment of hypertension in the elderly. J Am Geriatr Soc. 1985;33:109-15.

4. Gibb WE, Malpas JS, Turner P, White RJ. Comparison of bethanidine, alpha-methyldopa, and reserpine in essential hypertension. Lancet. 1970;2:275-7.

5. Segal MS. Bronchospasm after reserpine. N Engl J Med. 1969;281:1426-7.

6. Atuk NO, Owen JA, Jr. Bronchospasm after reserpine. N Engl J Med. 1969;281:908-9.

7. Diamond L. Drug-induced bronchospasm. J Clin Pharmacol J New Drugs. 1970;10:215-6.

8. Kirschenbaum HL, Rosenberg JM. What to look out for with guanethidine and reserpine. RN. 1984;47:31-3.

9. Pfeifer HJ, Greenblatt DK, Koch-Wester J. Clinical toxicity of reserpine in hospitalized patients: a report from the Boston Collaborative Drug Surveillance Program. Am J Med Sci. 1976;271:269-76.

10. Bacher NM, Lewis HA. Reserpine and tardive dyskinesia. Am J Psychiatry. 1984;141:719.

11. Dilsaver SC, Greden JF. Possible cholinergic mechanism in reserpine and tardive dyskinesia. Am J Psychiatry. 1984;141:151-2.

12. Peters HA. Questioning reserpine's adverse effect on tardive dyskinesia. Am J Psychiatry. 1983;140:1106.

13. Donatelli A, Geisen L, Feuer E. Case report of adverse effect of reserpine on tardive dyskinesia. Am J Psychiatry. 1983;140:239-40.

14. Murayama M, Yasuda K, Minamori Y, Mercado-Asis LB, Yamakita N, Miura K. Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation. J Clin Endocrinol Metab. 1992;75:935-42.

15. Ross RT. Drug-induced parkinsonism and other movement disorders. Can J Neurol Sci. 1990;17:155-62.

16. Berlant JL. Neuroleptics and reserpine in refractory psychoses. J Clin Psychopharmacol. 1986;6:180-4.

17. Reus VI. Behavioral side effects of medical drugs. Prim Care. 1979;6:283-94.

18. Goodwin FK, Bunney WE, Jr. Depressions following reserpine: a reevaluation. Semin Psychiatry. 1971;3:435-48.

19. Mackay EV, Khoo SK. Clinical and laboratory study of a new diuretic agent ("vectren") in pregnancy: a comparison with a diuretic agent in current use ("enduron"). Med J Aust. 1969;1:607-12.

20. Soghikian K, Bartenbach DE. Influence of dosage and duration of therapy on the rate of response to methyclothiazide in essential hypertension. South Med J. 1977;70:1397-404.

21. Black HR, Chrysant SG, Curry CL, Frishman WH, Grimm RH, Lasseter KC, Okun R, Pool JL, Raizada V, Vlachakis ND, et al. Antihypertensive and metabolic effects of concomitant administration of terazosin and methyclothiazide for the treatment of essential hypertension. J Clin Pharmacol. 1992;32:351-9.

22. Kennedy CC, Spiekerman RE, Elveback L. Antihypertensive properties of cryptenamine used with reserpine and methyclothiazide. J Pharm Sci. 1971;60:1139-41.

23. Product Information. Diutensen-R (methyclothiazide-reserpine). Wallace Laboratories. PROD.

24. Bryant JM, Schwartz N, Fletcher L, et al. Clinical studies of the antihypertensive effects of a new benzothiadiazine diuretic. Curr Ther Res Clin Exp. 1961;3:1-4.

25. Fleishman M. Letter: Reserpine, ECT, and depression. Am J Psychiatry. 1975;132:1088.

26. Lewis WH. Iatrogenic psychotic depressive reaction in hypertensive patients. Am J Psychiatry. 1971;127:1416-7.

27. Sharon E, Paolino JS, Kaplan D. Hematemesis after reserpine for Raynaud's phenomenon. Ann Intern Med. 1972;77:479-80.

28. Blumenthal M, Davis R, Doe RP. Carcinoid syndrome following reserpine therapy in thyrotoxicosis. Arch Intern Med. 1965;116:819-23.

29. Widmer RB. Reserpine: the maligned antihypertensive drug. J Fam Pract. 1985;20:81-3.

30. Kent TA, Wilber RD. Reserpine withdrawal psychosis: the possible role of denervation supersensitivity of receptors. J Nerv Ment Dis. 1982;170:502-4.

31. Samuels AH, Taylor AJ. Reserpine withdrawal psychosis. Aust N Z J Psychiatry. 1989;23:129-30.

32. Ambrosino SV. Depressive reactions associated with reserpine. N Y State J Med. 1974;74:860-4.

33. Labeeuw M, Pozet N, Aissa AH, Zech PY, Sassard J, Laville M. Uric acid renal handling: spontaneous changes and influence of a thiazide alone or associated with triamterene. Int J Clin Pharmacol Ther Toxicol. 1988;26:79-83.

34. Luther RR, Glassman HN, Estep CB, Maurath CJ, Jordan DC. The effects of terazosin and methyclothiazide on blood pressure and serum lipids. Am Heart J. 1989;117:842-7.

35. Combs RM. Unusual response to reserpine in paroxysmal atrial tachycardia with block unassociated with digitalis. South Med J. 1967;60:839-42.

36. Dillon PT, Babe J, Meloni CR, Canary JJ. Reserpine in thyrotoxic crisis. N Engl J Med. 1970;283:1020-3.

37. Entrican JH, Denburg JA, Gauldie J, Kelton JG. Angioimmunoblastic lymphadenopathy associated with reserpine. Lancet. 1984;2:820-1.

38. Mack TM, Henderson BE, Gerkins VR, et al. Reserpine and breast cancer in a retirement community. N Engl J Med. 1975;292:1366-71.

39. Curb JD, Hardy RJ, Labarthe DR, Borhani NO, Taylor JO. Reserpine and breast cancer in the Hypertension Detection and Follow- Up Program. Hypertension. 1982;4:307-11.

40. Labarthe DR, O'Fallon WM. Reserpine and breast cancer. A community-based longitudinal study of 2,000 hypertensive women. JAMA. 1980;243:2304-10.

41. Jick H. Editorial: Reserpine and breast cancer: a perspective. JAMA. 1975;233:896-7.

42. Newball HH, Byar DP. Does reserpine increase prolactin and exacerbate cancer of prostate? Case control study. Urology. 1973;2:525-9.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.