A depot injection, also known as a long-acting injectable (LAI), is a term for an

injection Injection or injected may refer to: Science and technology * Injective function, a mathematical function mapping distinct arguments to distinct values * Injection (medicine), insertion of liquid into the body with a syringe * Injection, in broadca ...

formulation of a medication which releases slowly over time to permit less frequent administration of a medication. They are designed to increase medication adherence and

consistency In deductive logic, a consistent theory is one that does not lead to a logical contradiction. A theory T is consistent if there is no formula \varphi such that both \varphi and its negation \lnot\varphi are elements of the set of consequences ...

, especially in patients who commonly forget to take their medicine. Depot injections can be created by modifying the drug molecule itself, as in the case of

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

s, or by modifying the way it is administered, as in the case of oil/lipid suspensions. Depot injections can have a duration of action of one month or greater and are available for many types of drugs, including

antipsychotic Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), p ...

s and

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

Purpose

Depot injections provide longer duration drug action through slow absorption into the bloodstream. They are usually administered in the muscle, into the skin, or under the skin. The injected medication slowly releases the medication into the bloodstream. It may be used in patients who forget to take their medication; some doctors and patients consider the use of a depot injection to be coercion, and are opposed to their use for that reason.

Mechanism

Drugs may be modified to be slowly activated by the body, or be absorbed slowly by the body. Many are dissolved in an organic oil, as the compound is

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

due to the addition of functional groups to provide slow action. An example of this is adding a functional group such as

decanoate Capric acid, also known as decanoic acid or decylic acid, is a saturated fatty acid, medium-chain fatty acid (MCFA), and carboxylic acid. Its formula is . Salts and esters of decanoic acid are called caprates or decanoates. The term capric aci ...

. The combination of an oil base and modification to decrease metabolic activation prevent medications from being fully released. This can result in length of activity of 2–4 weeks or more. The alteration of the

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of the drug (the absorption and activation) does not change the side effect profile of the medication; thus,

atypical antipsychotics The atypical antipsychotics (AAP), also known as second generation antipsychotics (SGAs) and serotonin–dopamine antagonists (SDAs), are a group of antipsychotic drugs (antipsychotic drugs in general are also known as tranquilizers and neuro ...

are still preferred over

typical antipsychotics Typical antipsychotics (also known as major tranquilizers, and first generation antipsychotics) are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis (in particular, schizophrenia). Typical antipsychotics m ...

Discovery

The first long-acting (depot) injections were antipsychotics

fluphenazine Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication. It is used in the treatment of chronic psychoses such as schizophrenia, and appears to be about equal in effectiveness to low-pot ...

and

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychos ...

. The concept of a depot injection arose before 1950, and originally was used to describe antibiotic injections that lasted longer to allow for less frequent administration.

Pharmacokinetics

Medroxyprogesterone acetate levels after a single intramuscular injection of different doses of medroxyprogesterone acetate in women

Most commonly, depot injections are designed to have a duration of 2–4 weeks of action, however the pharmacokinetics of a specific formulation vary. Absorption and metabolism can both be affected by modifying the drug itself (for example, by attaching a

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

) or by the formulation of the product (examples are oil or

microsphere Microparticles are particles between 0.1 and 100 μm in size. Commercially available microparticles are available in a wide variety of materials, including ceramics, glass, polymers, and metals. Microparticles encountered in daily life includ ...

preparations). Repeated administration of depot injections can lead to a half life over one month (as in some preparations of

), but this can be variable in different patients. Hormonal depot injections of

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

can last anywhere from one week to over one month.

Medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of ...

is available as a depot injection which is injected once every three months to provide continuous hormonal contraception and releases for up to nine months after injection.

Availability

Many medications are available as depot injections, including many typical and atypical antipsychotics, as well as some

hormonal medication A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones are ...

s and medication for

opioid use disorder Opioid use disorder (OUD) is a substance use disorder characterized by cravings for opioids, continued use despite physical and/or psychological deterioration, increased tolerance with use, and withdrawal symptoms after discontinuing opioids. ...

. Depot injections of antipsychotics are used to improve historically low adherence in patients with diseases such as

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 ...

. Different products may be administered or implanted either by a doctor or nurse, while some are designed to be administered by the patient themselves. Self-administered depot injections are used to increase healthcare access and decrease the need to visit the doctor as frequently, especially in

low and middle income countries A developing country is a sovereign state with a less-developed industrial base and a lower Human Development Index (HDI) relative to developed countries. However, this definition is not universally agreed upon. There is also no clear agreemen ...

Insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

may also be considered a depot injection depending on formulation.

Insulin glargine Insulin glargine sold under the brand name Lantus among others is a long-acting modified form of medical insulin, used in the management of type 1 and type 2 diabetes. It is injected just under the skin. Effects generally begin an hour af ...

, for example, is designed to precipitate after injection so it can be slowly absorbed by the body over a longer period than

regular insulin Regular insulin, also known as neutral insulin and soluble insulin, is a type of short-acting medical insulin. It is used to treat type 1 diabetes, type 2 diabetes, gestational diabetes, and complications of diabetes such as diabetic ketoaci ...

would be. Depot injections of insulins have been studied to better replicate the body's natural basal rate of insulin production, and which can be activated by light to control the release of insulin from the injected depot.

References