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RELIS database 2000; 166, RELIS Nord-Norge

Dato for henvendelse: 28.03.2000

  • RELIS Nord-Norge

  • Utredningen er utarbeidet på grunnlag av tilgjengelig litteratur og ressurser på publiseringstidspunktet. Innholdet i utredningen oppdateres ikke etter publisering. Helsepersonell er selv ansvarlig for bruk av utredningens innhold i rådgivning eller pasientbehandling.

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The abuse potential of anticholinergic agents

Dato for henvendelse: 28.03.2000

RELIS database 2000; 166, RELIS Nord-Norge.

SPØRSMÅL: The abuse potential of the three available anticholinergic agents (benztropine, biperiden and orphenadrine) was questioned. The following review attempts to answer this.

SVAR: Anticholinergic drugs have been prescribed for many years for the symptomatic treatment of Parkinson's disease and the extrapyrimidal side effects (EPSE's) of some antipsychotics.
A review of the literature identified a number of cases reporting anticholinergic drug abuse by some patients to achieve pleasurable effects ranging from mild euphoria to toxic antichloinergic psychosis (1-13).Two reviews of the abuse of anticholinergics (14,15), and one study attempting to distinguish use or abuse of anticholinergics were identified (16).

The cases, in conjunction with the two reviews on anticholinergic abuse, can be subdivided into three groups. 1. True abusers, people who take anticholinergic drugs for there euphoric or psychotic effects without a valid medical reason are seldom (11,13). 2. Abusers with valid medical reasons, who were prescribed anticholinergics for the management of EPSE's, and now consume them in an abusive manner. Reasons for abuse vary, however most seek an euphoric or "buzz" effect. They obtain the drug in a variety of ways. These include, illegally purchasing them on the black market, requesting dose increases, feigning EPSE's and losing their prescription (3-12).
3. Patients who potentially benefit from Anticholinergic drugs. These patients have a valid medical indication for anticholinergics, and use their medication as prescribed. They are labelled as abusers because they voice opposition to stopping their anticholinergics (9,11). It is not clear, however, if these patients have chronic EPS and fear its return and thus require their medication.

A study by Saran evaluated 108 patients with schizophrenia to identify differences between patients with a real ongoing need for anticholinergics from those who were abusing them (16). Methodological limitations of this study exist. No conclusions can be drawn as to frequency and characteristcs of abuse of anticholinergics.

All of the cases reported were anecdotal and discriptive. Most cases did not disclose any information on abuse of other substances. Some patients practice polypharmacy abuse. Several classes of drugs of abuse, in addition to muscarinic agents, antagonise and therefore up-regulate and supersensitise muscarinic cholinergic systems. (11,16). These drugs include cannabinoids, barbiturates, opiates and ethanol (14). It is thus difficult to establish if the anticholinergic drug, in the presence of either of these classes of drug, has an euphoric effect. It has been reported that the CNS toxicity and regulation of mood and effect results from cholinergic inhibition (14), a question also arises as to whether this might be the result of some other effect of the drug.

The dose of anticholinergic involved in many of the cases of abuse, was not quoted. Toxic reactions have been reported in psychiatric patients who received anticholinergics in normal doses in conjunction with phenothiazines (11,17). It has also been suggested that narcotic users may be particularly sensitive to small doses of anticholinergic agent because narcotics can diminish the rate of release of acetylcholine from nerve endings in both peripheral and central nerve endings (11). Thus the dose separating treatment, euphoric and toxic levels is dependant on individual susceptibility and concurrent medication.

Akinesia alone may cause demoralisation (9). It is possible that the subjective euphoria is the psychological consequence of relief of akinesia (an extrapyramidal side-effect to antipsychotic medication) by anticholinergic medication.

It appears from the case reports, that all three anticholinergics (available in Norway) are equally abused. It has been suggested that benztropine may be least abused (8). Benzhexol (not available in Norway) has been involved more than any other drug in the reports and several authors have suggested that it may have a greater potential for abuse (3,4,10,14). However these preferences do not distinguish between real differences in their mood elevating properties or current prescribing patterns and hence availability.

It has been suggested that anticholinergic drugs can produce psychological or physiological dependance (14). This is possibly based on the fact that drug-seeking behaviour can be associated with misuse of anticholinergics, patients often refuse to withdraw their treatment, and withdrawal of these substances may result in anxiety, insomnia, diaphoresis, malaise, dysphoria and exacerbation of motor function (15, 18-20).

Two studies support these theories, but are inconclusive due to methodological limitations (18,19).
Sudden withdrawal of anticholinergics may precipitate symptoms of cholinergic rebound, notably nausea, diaphoresis, restlesseness and insomnia (20). The possible euphoric effects of these drugs may also contribute to the development of dependancy.

It is difficult to establish whether anticholinergics are truly abused for their euphoric effects. Considering how often anticholinergics are prescribed, there are few case reports. It is difficult to distinguish between cholinergic withdrawal symptoms and other symptoms controlled by anticholinergics drugs. Overall it is not possible to distinguish which anticholinergic drug has the greatest abuse potential.

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