Combination therapy or polytherapy is

therapy A therapy or medical treatment (often abbreviated tx, Tx, or Tx) is the attempted remediation of a health problem, usually following a medical diagnosis. As a rule, each therapy has indications and contraindications. There are many differe ...

that uses more than one

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the medical field and ...

or modality. Typically, the term refers to using multiple therapies to treat a ''single''

disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

, and often all the therapies are pharmaceutical (although it can also involve non-medical therapy, such as the combination of medications and talk therapy to treat depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where available,

dosage form Dosage forms (also called unit doses) are pharmaceutical drug products in the form in which they are marketed for use, with a specific mixture of active ingredients and inactive components (excipients), in a particular configuration (such as a ca ...

s that contain more than one active ingredient (such as fixed-dose combinations).

Polypharmacy Polypharmacy (polypragmasia) is the simultaneous use of multiple medicines by a patient for their conditions. Most commonly it is defined as regularly taking five or more medicines but definitions vary in where they draw the line for the minimum ...

is a related term, referring to the use of multiple medications (without regard to whether they are for the same or separate conditions/diseases). Sometimes "polymedicine" is used to refer to pharmaceutical combination therapy. Most of these kinds of terms lack a universally consistent definition, so caution and clarification are often advisable.

Uses

Conditions treated with combination therapy include

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...

leprosy Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria '' Mycobacterium leprae'' or '' Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve d ...

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...

, and HIV/

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

. One major benefit of combination therapies is that they reduce development of

drug resistance Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...

since a pathogen or tumor is less likely to have resistance to multiple drugs simultaneously.

Artemisinin Artemisinin () and its semisynthetic derivatives are a group of drugs used in the treatment of malaria due to '' Plasmodium falciparum''. It was discovered in 1972 by Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine for h ...

-based monotherapies for malaria are explicitly discouraged to avoid the problem of developing resistance to the newer treatment. Combination therapy may seem costlier than monotherapy in the short term, but when it is used appropriately, it causes significant savings: lower treatment failure rate, lower case-fatality ratios, fewer side-effects than monotherapy, slower development of resistance, and thus less money needed for the development of new drugs.

In oncology

Combination therapy has gained momentum in oncology in recent years, with various studies demonstrating higher response rates with combinations of drugs compared to monotherapies, and the FDA recently approving therapeutic combination regimens that demonstrated superior safety and efficacy to monotherapies. In a recent study about solid cancers,

Martin Nowak Martin Andreas Nowak (born April 7, 1965) is an Austrian-born professor of mathematical biology, at Harvard University since 2003. He is one of the leading researchers in the field that studies the role of cooperation in evolution. Nowak has hel ...

Bert Vogelstein Bert Vogelstein (born 1949) is director of the Ludwig Center, Clayton Professor of Oncology and Pathology and a Howard Hughes Medical Institute investigator at The Johns Hopkins Medical School and Sidney Kimmel Comprehensive Cancer Center. A pio ...

, and colleagues showed that in most clinical cases, combination therapies are needed to avoid the evolution of resistance to targeted drugs. Furthermore, they find that the simultaneous administration of multiple targeted drugs minimizes the chance of relapse when no single mutation confers cross-resistance to both drugs. Various systems biology methods must be used to discover combination therapies to overcome drug resistance in select cancer types. Recent

precision medicine Precision, precise or precisely may refer to: Science, and technology, and mathematics Mathematics and computing (general) * Accuracy and precision, measurement deviation from true value and its scatter * Significant figures, the number of digi ...

approaches have focused on targeting multiple biomarkers found in individual tumors by using combinations of drugs. However, with 300 FDA-approved cancer drugs on the market, there almost 45,000 possible two-drug combinations and almost 4.5 million three-drug combinations for to choose from. That level of complexity is one of the primary impediments to the growth of combination therapy in oncology. T has recently highlighted combination therapy as a top research priority in oncology.

Bacterial infections

Combination therapy with two or more antibiotics are often used in an effort to treat multi-drug resistant Gram-negative bacteria.

Contrast to monotherapy

Monotherapy, or the use of a single therapy, can be applied to any therapeutic approach, but it is most commonly used to describe the use of a single

. Normally, monotherapy is selected because a single medication is adequate to treat the medical condition. However, monotherapies may also be used because of unwanted side effects or dangerous

drug interaction Drug interactions occur when a drug's mechanism of action is disturbed by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often the inhibition of the specific receptors available to the drug, ...

References

External links