Cyproheptadine, sold under the brand name Periactin among others, is a first-generation

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

with additional

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

, antiserotonergic, and

local anesthetic A local anesthetic (LA) is a medication that causes absence of all sensation (including pain) in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensati ...

properties. It was patented in 1959 and came into medical use in 1961. In 2022, it was the 293rd most commonly prescribed medication in the United States, with more than 400,000 prescriptions.

Medical uses

Cyproheptadine is used to treat allergic reactions (specifically

hay fever Allergic rhinitis, of which the seasonal type is called hay fever, is a type of rhinitis, inflammation in the nose that occurs when the immune system overreacts to allergens in the air. It is classified as a Allergy, type I hypersensitivity re ...

). There is evidence supporting its use for allergies, but second generation antihistamines such as

ketotifen Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives). Ketotifen is available in ophthalmic (eye drops or drug-eluting contact lenses) and o ...

and

loratadine Loratadine, sold under the brand name Claritin among others, is a medication used to treat allergies. This includes allergic rhinitis (hay fever) and hives. It is also available in drug combinations such as loratadine/pseudoephedrine, in whic ...

have shown equal results with fewer side effects. It is also used as a preventive treatment against

migraine Migraine (, ) is a complex neurological disorder characterized by episodes of moderate-to-severe headache, most often unilateral and generally associated with nausea, and light and sound sensitivity. Other characterizing symptoms may includ ...

. In a 2013 study the frequency of migraine was dramatically reduced in patients within 7 to 10 days after starting treatment. The average frequency of migraine attacks in these patients before administration was 8.7 times per month, this was decreased to 3.1 times per month at 3 months after the start of treatment. This use is on the label in the UK and some other countries. It is also used off-label in the treatment of cyclical vomiting syndrome in infants; the only evidence for this use comes from retrospective studies. Cyproheptadine is sometimes used off-label to improve

akathisia Akathisia (IPA: /æ.kə.ˈθɪ.si.ə/) is a movement disorder characterized by a subjective feeling of inner restlessness accompanied by mental distress and/or an inability to sit still. Usually, the legs are most prominently affected. Those a ...

in people on antipsychotic medications. It is used off-label to treat various dermatological conditions, including psychogenic itch, drug-induced

hyperhidrosis Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...

(excessive sweating), and prevention of blister formation for some people with

epidermolysis bullosa simplex Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.Freedberg, et al. (2003). ''Fitzpatrick's Dermatology in General Medicine''. (6th ed.). McGraw-Hill. . It is one of the major f ...

. One of the effects of the drug is increased

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to reg ...

and weight gain, which has led to its use (off-label in the USA) for this purpose in children who are wasting as well as people with

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

. It is also used off-label in the management of moderate to severe cases of

serotonin syndrome Serotonin syndrome (SS) is a group of symptoms that may occur with the use of certain Serotonin, serotonergic medications or Recreational drug use, drugs. The symptoms can range from mild to severe, and are potentially fatal. Symptoms in mild c ...

, a complex of symptoms associated with the use of serotonergic drugs, such as

selective serotonin reuptake inhibitor Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by blo ...

s (and

monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espe ...

), and in cases of high levels of serotonin in the blood resulting from a serotonin-producing carcinoid tumor. Cyproheptadine has sedative effects and can be used to treat

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

similarly to other centrally-acting antihistamines. The recommended dose for this use is 4 to 8 mg.

Adverse effects

Adverse effects include: * Sedation and sleepiness (often transient) * Dizziness * Disturbed coordination * Confusion * Restlessness * Excitation * Nervousness * Tremor * Irritability * Insomnia * Paresthesias * Neuritis * Convulsions * Euphoria * Hallucinations * Hysteria * Faintness * Allergic manifestation of rash and edema * Diaphoresis * Urticaria * Photosensitivity * Acute labyrinthitis * Diplopia (seeing double) * Vertigo * Tinnitus * Hypotension (low blood pressure) * Palpitation * Extrasystoles * Anaphylactic shock * Hemolytic anemia * Blood dyscrasias such as

leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...

agranulocytosis Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous lowered white blood cell count (leukopenia, most commonly of neutrophils) and thus causing neutropenia in the circulating blood. I ...

and

thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...

* Cholestasis * Hepatic (liver) side effects such as: **

Hepatitis Hepatitis is inflammation of the liver parenchyma, liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), Anorexia (symptom), poor appetite ...

Jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

Liver failure Liver failure is the inability of the liver to perform its normal synthetic and metabolic functions as part of normal physiology. Two forms are recognised, acute and chronic (cirrhosis). Recently, a third form of liver failure known as acute- ...

** Hepatic function abnormality *

Epigastric In anatomy, the epigastrium (or epigastric region) is the upper central region of the abdomen. It is located between the costal margins and the subcostal plane. Pain may be referred to the epigastrium from damage to structures derived from the fo ...

distress *

Anorexia Anorexia nervosa (AN), often referred to simply as anorexia, is an eating disorder characterized by Calorie restriction, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. Individuals wit ...

* Nausea * Vomiting * Diarrhea *

Anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

side effects such as: ** Blurred vision ** Constipation ** Xerostomia (dry mouth) ** Tachycardia (high heart rate) ** Urinary retention ** Difficulty passing urine ** Nasal congestion ** Nasal or throat dryness * Urinary frequency * Early menses * Thickening of bronchial secretions * Tightness of chest and wheezing * Fatigue * Chills * Headache * Increased appetite * Weight gain

Overdose

Gastric decontamination measures such as

activated charcoal "Activated" is a song by English singer Cher Lloyd. It was released on 22 July 2016 through Vixen Records. The song was made available to stream exclusively on ''Rolling Stone'' a day before to release (on 21 July 2016). Background In an inter ...

are sometimes recommended in cases of overdose. The symptoms are usually indicative of CNS depression (or conversely CNS stimulation in some) and excess anticholinergic side effects. The LD₅₀ in mice is 123 mg/kg and 295 mg/kg in rats.

Pharmacology

Pharmacodynamics

Cyproheptadine is a very potent

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

of the H₁ receptor. At higher concentrations, it also has

, antiserotonergic, and antidopaminergic activities. Of the

serotonin receptor 5-HT receptors, 5-hydroxytryptamine receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in multiple tissues including the central and peripheral nervous systems. They mediate both ex ...

s, it is an especially potent antagonist of the 5-HT₂ receptors. This is thought to underlie its effectiveness in the treatment of

. However, it is possible that blockade of 5-HT₁ receptors may also contribute to its effectiveness in serotonin syndrome. Cyproheptadine has been reported to block 85% of 5-HT₂ receptors in the human brain at a dose of 4 mg three times per day (12 mg/day total) and to block 95% of 5-HT₂ receptors in the human brain at a dose of 6 mg three times per day (18 mg/day total) as measured with

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

(PET). The dose of cyproheptadine recommended to ensure blockade of the 5-HT₂ receptors for serotonin syndrome is 20 to 30 mg. Blockade of the serotonin 5-HT_2B receptor may be specifically involved in the antimigraine effects of cyproheptadine. Besides its activity at

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

targets, cyproheptadine has been reported to possess weak

antiandrogen Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking t ...

ic activity.

Pharmacokinetics

Cyproheptadine is well-absorbed following oral ingestion, with peak plasma levels occurring after 1 to 3 hours. Its terminal half-life when taken orally is approximately 8 hours.

Chemistry

Cyproheptadine is a tricyclic benzocycloheptene and is closely related to pizotifen and

as well as to

tricyclic antidepressant Tricyclic antidepressants (TCAs) are a class of medications that are used primarily as antidepressants. TCAs were discovered in the early 1950s and were marketed later in the decade. They are named after their chemical structure, which contains ...

Research

Cyproheptadine was studied in one small trial as an adjunct in people with

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

whose condition was stable and were on other medication; while attention and verbal fluency appeared to be improved, the study was too small to draw generalizations from. It has also been studied as an adjuvant in two other trials in people with schizophrenia, around fifty people overall, and did not appear to have an effect. There have been some trials to see if cyproheptadine could reduce sexual dysfunction caused by

(SSRI) and antipsychotic medications. Cyproheptadine has been studied for the treatment of

post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a mental disorder that develops from experiencing a Psychological trauma, traumatic event, such as sexual assault, domestic violence, child abuse, warfare and its associated traumas, natural disaster ...

Veterinary use

Cyproheptadine is used in cats as an

appetite stimulant An orexigenic, or appetite stimulant, is a drug, hormone, or chemical compound, compound that increases appetite and may induce hyperphagia. This can be a medication or a naturally occurring neuropeptide hormone, such as ghrelin, orexin or neuropep ...

and as an adjunct in the treatment of

asthma Asthma is a common long-term inflammatory disease of the airways of the lungs. It is characterized by variable and recurring symptoms, reversible airflow obstruction, and easily triggered bronchospasms. Symptoms include episodes of wh ...

. Retrieved on 26 October 2008. Possible adverse effects include excitement and aggressive behavior. Retrieved on 26 October 2008. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of cyproheptadine in cats is 12 hours. Cyproheptadine is a second line treatment for pituitary pars intermedia dysfunction in horses.

References

{{Authority control 5-HT2 antagonists Antiandrogens Antihistamines Antipsychotics Appetite stimulants Dibenzocycloheptenes Dopamine antagonists Hallucinogen antidotes Local anesthetics M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Piperidines Serotonin receptor antagonists Sodium channel blockers