Earn CME/CE in your profession:

Continuing Education Activity

Reserpine is a medication used in managing and treating hypertension, which is a significant risk factor for cardiovascular disease. It is an adrenergic uptake inhibitor. This activity reviews the indications, contraindications, mechanism of action, adverse effects, and other vital factors pertinent for interprofessional team members in the care of patients with hypertension and related conditions.


  • Describe the mechanism of action of reserpine.
  • Review the potential adverse effects of reserpine.
  • Identify the indications for reserpine therapy.
  • Outline the importance of collaboration and communication amongst the interprofessional team to enhance care delivery for patients receiving antihypertensive therapy with reserpine.


Reserpine is an indole alkaloid extracted from Rauwolfia serpentine roots, an Indian climbing shrub. Reserpine has FDA approval since 1955 and is one of the first agents developed to treat hypertension in clinical practice. Reserpine can be prescribed alone or combined with a vasodilator or thiazide diuretic, such as reserpine-hydrochlorothiazide, as commonly used in China for over 40 years.[1][2] Reserpine was utilized as a first-line antihypertensive therapy when initially introduced but is currently considered second-line treatment.[3] This change in status is due to newer and more favorable antihypertensive medications with better side effects.

A recent clinical trial tested the effects of reserpine on refractory hypertension (RfHTN) or uncontrolled blood pressure after ≥ five antihypertensive medications from different classes. Out of 45 patients with suspected RfHTN, seven consented to participate in the clinical trial, which only six patients were able to complete.[4] For the trial, patients tapered and discontinued all sympatholytic medications before administering reserpine 0.1 mg daily for four weeks.[4] Treatment results indicate that reserpine is a potent sympatholytic agent that can lower blood pressure in patients who had unsuccessful maximal antihypertensive therapy.[4]

In the 1960s, reports indicated that depression correlated with the monoamine-depleting activity of reserpine treatment, and a neurochemical model of depression was subsequently developed.[5] Recent studies examined the association between reserpine and its depressogenic effect. A case-control, cross-sectional study was conducted from August 2018 to December 2018 to examine the correlation between low-dose reserpine use and depression in Chinese hypertensive patients at the age of 60 and over, with the mean age at 70.3 years.[6] The study utilized the Zung Self-Rating Depression Scale to develop a Chinese depression scale to measure depressive symptoms in 787 reserpine users and 787 non-reserpine users. Researchers found no statistical significance in the prevalence of mild, moderate, or severe depression between reserpine users and non-reserpine users.[6] However, it is important to note that there are limitations to this study, which include utilizing a self-rating depression scale.[6]

Reserpine has historically had other uses. Reserpine was previously utilized to treat schizophrenia and tardive dyskinesia; however, it is not currently in clinical practice for these indications.[7]

Mechanism of Action

Reserpine functions as a sympatholytic agent and antihypertensive medication by acting as an adrenergic uptake inhibitor. Reserpine binds to the storage vesicles of catecholamines, such as dopamine and norepinephrine. Specifically, reserpine irreversibly blocks VMAT-2 (vesicular monoamine transporter-2) in the adrenergic neurotransmission pathway.[8] The inhibition of catecholamine pumps results in blockage of the uptake of serotonin, norepinephrine, and dopamine into presynaptic storage vesicles. This action will then lead to their depletion by cytoplasmic monoamine oxidase from peripheral and central synapses.[3] Reserpine is lipid-soluble, so it can cross the blood-brain barrier and slow the activity of the nervous system, resulting in decreased heart rate, decreased cardiac output, decreased peripheral resistance, and lowered blood pressure.[6] The main effector regions are the cardiovascular system, central nervous system, and gastrointestinal tract.


Administration of Reserpine

 For hypertension:

  • Adults – Orally: Start initially at 0.5 mg, once a day with or without food, for 1 or 2 weeks. For maintenance, reduce to 0.05 to 0.25 mg daily.
  • Pediatric – Usually not recommended. If used; orally: start initially at 20 mcg daily; maximum dose at 0.25 mg daily.

For psychiatric disorders (not typically used):

  • Orally: 0.5 mg once a day, but may range from 0.1 to 1 mg depending on patient response

Adverse Effects

Side effects commonly occur when patients have taken tricyclic anti-depressants are administered before starting reserpine.

Common adverse reactions:

  • Nasal congestion
  • Dizziness
  • Drowsiness
  • Depression
  • Headache
  • Nausea
  • Vomiting
  • Diarrhea
  • Loss of appetite
  • Dry mouth
  • Arrhythmias
  • Syncope
  • Male impotence
  • Gastrointestinal upset

 Severe adverse effects:

  • Bradycardia
  • Chest pain
  • Hypotension
  • Gastric ulceration


Absolute contraindications for reserpine use include the presence of:

  • Active peptic ulcer
  • Ulcerative colitis
  • Electroconvulsive therapy
  • Pregnancy
  • Parkinson’s disease
  • Rauwolfia alkaloid hypersensitivity
  • Psychiatric depression
  • Pheochromocytoma

Caution is necessary when administering reserpine to patients with a history of a peptic ulcer or gastroesophageal reflux disease (GERD) due to a possible side effect of increased gastric acid secretion.[9] At higher doses, reserpine may cause a significant incidence of mental depression, anxiety, or psychosis. The FDA categorizes reserpine as a Pregnancy C class drug.  

Relative contraindications for reserpine use include the presence of:

  • Cardiac arrhythmias
  • Myocardial infarction
  • Renal insufficiency
  • Asthma
  • Elderly patients

For relative contraindications, reserpine use should be approached with caution and begin with lower doses.


Reserpine administered via the oral route is rapidly absorbed, reaching its peak concentration level after approximately 2 hours. Reserpine has a bioavailability of approximately 50% to 70% and an elimination half-life of 11.5 days. Administering reserpine beyond the upper dosage limit can lead to central nervous system depression, bradycardia, hypotension, lethargy, and coma. Reserpine is assigned Pregnancy Category C.

There are currently no recommended routine tests or laboratory analyses for monitoring the use of reserpine.


Symptoms from reported cases of reserpine poisoning include hypotension, nausea, vomiting, sedation, coma, cardiovascular collapse, and death, while the latter two are uncommon.[10]

After ingestion, toxicity symptoms will develop over the initial 4 hours and generally resolve around 18 to 24 hours.

If the patient is experiencing gastric hyperacidity, H2-histamine receptor antagonists or atropine are therapeutic options. Gastrointestinal decontamination may also be an option.

There have been no signs of clinically apparent liver injury with reserpine use.

Enhancing Healthcare Team Outcomes

The collaboration of multiple healthcare professionals is necessary to enhance patient-centered care in reserpine treatment. Every interprofessional team member needs to understand the mechanism of action of reserpine, proper dosage administration, adverse effects, and toxicity treatment to provide proper care for patients. Every team member has a role, from the physician who prescribes the drug to the pharmacist who provides the appropriate dosing. Understanding the side effects and knowing the timing of ingestion will help the healthcare team monitor possible toxicity and plan for treatment. If the nurse notices any adverse effects or signs of toxicity, he/she will have to report the findings to the physician and pharmacist to determine the best course of action to stabilize the patient. The clinician would have to consult with the pharmacist regarding the use of activated charcoal if the ingestion of reserpine was within a few hours. Once the patient stabilizes, the healthcare team must work together to determine the cause and reason for toxicity. The team should monitor the patient until all signs of toxicity have dissipated. Depending on the cause of overdose or toxicity, the healthcare team may have to consider a different medication to replace reserpine.

An integrated interprofessional team approach with collaborative decision making, mutual respect, and communication with the patient are vital elements to enhance team performance and improve patient-centered care. [Level 5]

Article Details

Article Author

Michelle Cheung

Article Editor:

Mayur Parmar


7/12/2022 4:34:24 PM

PubMed Link:




Griebenow R,Pittrow DB,Weidinger G,Mueller E,Mutschler E,Welzel D, Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Blood pressure. 1997 Sep;     [PubMed PMID: 9360001]


Li S,Liu X,Li L, A Multicenter Retrospective Analysis on Clinical Effectiveness and Economic Assessment of Compound Reserpine and Hydrochlorothiazide Tablets (CRH) for Hypertension. ClinicoEconomics and outcomes research : CEOR. 2020;     [PubMed PMID: 32104022]


Shamon SD,Perez MI, Blood pressure-lowering efficacy of reserpine for primary hypertension. The Cochrane database of systematic reviews. 2016 Dec 21;     [PubMed PMID: 27997978]


Siddiqui M,Bhatt H,Judd EK,Oparil S,Calhoun DA, Reserpine Substantially Lowers Blood Pressure in Patients with Refractory Hypertension: A Proof of Concept Study. American journal of hypertension. 2020 Mar 17;     [PubMed PMID: 32179903]


Park BK,Kim YR,Kim YH,Yang C,Seo CS,Jung IC,Jang IS,Kim SH,Lee MY, Antidepressant-Like Effects of {i}Gyejibokryeong-hwan{/i} in a Mouse Model of Reserpine-Induced Depression. BioMed research international. 2018;     [PubMed PMID: 30046601]


Zhu GH,Sun XP,Li J,Pi L,Tang HQ,Gao HQ,Cong HL,Qu P,Lu XZ,Zhang XJ,Zhao LS,Guo YF,Liu DX,Zhang LQ,Tang H,Hu YX,Fan L,Hua Q, No association between low-dose reserpine use and depression in older hypertensive patient: result of a multicenter, cross-sectional study. Journal of geriatric cardiology : JGC. 2019 Aug;     [PubMed PMID: 31555328]


El-Sayeh HG,Rathbone J,Soares-Weiser K,Bergman H, Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia. The Cochrane database of systematic reviews. 2018 Jan 18;     [PubMed PMID: 29342497]


Leão AH,Meurer YS,da Silva AF,Medeiros AM,Campêlo CL,Abílio VC,Engelberth RC,Cavalcante JS,Izídio GS,Ribeiro AM,Silva RH, Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression. Frontiers in aging neuroscience. 2017;     [PubMed PMID: 28396635]


Yi R,Wang R,Sun P,Zhao X, Antioxidant-mediated preventative effect of Dragon-pearl tea crude polyphenol extract on reserpine-induced gastric ulcers. Experimental and therapeutic medicine. 2015 Jul;     [PubMed PMID: 26170959]


Lobay D, Rauwolfia in the Treatment of Hypertension. Integrative medicine (Encinitas, Calif.). 2015 Jun;     [PubMed PMID: 26770146]