Benzodiazepines (BZDs), or minor tranquilizers, are medications indicated for the short-term treatment of anxiety and insomnia. They also have other uses, such as muscle relaxants and antiepileptic drugs.
Their main limitation in psychiatry is the attachment that people develop to these medications, for two reasons: their rapid effect on symptoms and, for some BZDs, their ability to induce abuse and addiction.
Prolonged use of BZDs induces tolerance, that is, a loss of their effects and an increased susceptibility to developing, in the event of abrupt discontinuation, a temporary syndrome characterized by symptoms “opposite” to those produced by BZDs. Depending on the dose and potency, BZD withdrawal syndrome can produce severe mental disturbances beyond anxiety, including psychotic symptoms such as delusions, hallucinations, and disorientation in space and time. Because of the risk of major epileptic seizures, BZD withdrawal syndrome, like alcohol withdrawal, to which it is chemically similar, can be fatal.
In theory, BZDs should not be taken for long periods. In practice, anxious patients often become tolerant to them precisely because they take them regularly, relying on their initially beneficial effect on anxiety. The psychological attachment is maintained even when the effect is no longer present, because a cyclical mechanism develops whereby anxiety increases several hours after the last dose, and taking the next dose promptly brings the anxiety back to normal. These phenomena, known as micro-withdrawal, are essentially an imperfect transition between two successive doses, but they maintain the belief that the medication is still necessary to control anxiety, especially when it is taken in the evening.
Furthermore, the brain tends to remember the initial rapid effect particularly clearly, so that even when the effect is no longer present, the first thought that comes to mind when anxiety returns is to take a BZD. People who have successfully tried other, more effective treatments for anxiety often do not return to those medications when they experience relapses, but instead go back to using BZDs.
In cases of discontinuation or recurrent micro-withdrawal, even several times a day, characteristic though sometimes subtle symptoms may occur: alternating drowsiness and nervousness/agitation, aggression, a state of hyperarousal, increased sensory perception with an unpleasant effect (blinding lights, excessively vivid or “liquid” colors, the need to wear sunglasses, sounds that feel excessively intense, hypersensitivity to touch, and intolerance to pain).
Prolonged use of short-acting BZDs produces a “highs and lows” pattern of effects, with end-of-dose anxiety (the aforementioned micro-withdrawal) and a series of side effects associated with chronic intoxication: memory impairment, impaired balance, slowed reflexes, muscle weakness and reduced exercise tolerance, muscle pain even at rest, irritability, and impulsivity (outbursts of anger, violent acts, and destructive behavior).
There is currently no indication for long-term BZD therapy, except in some treatment-resistant cases. BZD addiction can be treated with clonazepam as an initial maintenance treatment; this is the only systematic indication for long-term use of a BZD (clonazepam), according to the same principle as methadone in relation to heroin: it is not a substitute treatment, but rather a treatment that normalizes the neurochemical system and the addictive behavior that has developed around it.
Using several BZDs together generally does not make much sense. If they are short-acting BZDs, this is equivalent to repeatedly taking the same medication. If they have different durations of action, more than one BZD ends up circulating in the body while they act on the same receptor system; therefore, if one works, the other does as well. In general, the one with greater affinity and a higher concentration will have the predominant effect.
BZD abuse and dependence have been extensively studied. Individuals who abuse BZDs generally take doses far higher than the initial doses, unlike patients with uncomplicated anxiety, who tend to continue taking the initial doses or only slightly higher ones. In general, people who abuse BZDs have previously had, or simultaneously have, a tendency to abuse other substances or alcohol (8 out of 10).
The risk of becoming dependent in the sense of developing drug addiction is related to several factors:
a) the duration and amount of the doses taken;
b) the type of BZD;
c) individual susceptibility to euphoric effects.
Chemically similar BZDs can have very different addictive potential. This does not depend on potency or duration of action so much as on the rapidity of onset, particularly when combined with medium-to-high potency. Preparations with rapid release are therefore the ones that create the greatest risk of this type of attachment.
A BZD addict exhibits the same behaviors as a person addicted to other substances: they binge on BZDs, are unable to reduce their intake, deny the negative aspects of use (chronic intoxication) or minimize them by attributing them to other causes; they seek to obtain the substance through lies, forged prescriptions, “under-the-table” arrangements with accommodating doctors and pharmacists, or simply by persistently insisting and sometimes threatening healthcare professionals in order to obtain prescriptions or larger quantities of medication.
Typically, they do not accept another BZD as a substitute, even if it has a longer duration of action and greater potency, and they continue using the BZD to which they are attached even when another BZD is administered at a dose sufficient to prevent withdrawal and block the effects of other BZDs taken simultaneously.
Among people who are addicted to drugs, some benzodiazepines, but not others, circulate on the black market and are known as “psychotropic drugs,” because among the various drugs they are the ones officially marketed as psychiatric medications.
Some products have been withdrawn from the market (flunitrazepam) because they were widely used as drugs of abuse, including as substances administered to unsuspecting victims for the purpose of robbery or sexual assault. Other molecules are currently included in special controlled-drug schedules, requiring non-repeatable prescriptions with limited validity, in order to discourage repeated prescribing without prior reassessment of the patient and to prevent indefinite use by patients who no longer return to see their doctor.