Addiction Treatment Blog

Separation Liability

Liability for drug induced injuries did not become an issue of general concern until quite recently. However, a number of drug-induced problems from thalidomide in the 1960s to Opren and diethylstilbestrol in the 1970s have caused widespread public disquiet and led to increasing awareness of issues to do with liability. In psychiatry, concern in the UK focuses on the question of benzodiazepine prescribing, while in the US the paramount issue concerns the occurrence of tardive dyskinesia in individuals taking neuroleptics. The question has become an emotive one with some commentators who survey the problem referring to the appalling frequency of drug-induced injury, while others comment on its astonishing tray (1). Whatever the absolute frequencies, contrary probably to public belief, the evidence suggests that the larger the pharmaceutical company, the better its practice regarding drug safety is likely to be (2).

Drug-induced problems may stem from toxic effects of a drug, or toxic effects caused by an impure additive, or from allergic reactions to the drug or its additive. Problems may also stem from over prescribing. For instance, in the case of someone who dies from a resistant bacterial infection, a relative could claim that the subject’s death arose in part from the excessive prescription of antibiotics that in its own right brings about the production of resistant infections. In the case of neuroleptics, problems may be brought about by the overuse of these drugs but this overuse, far from being solely promoted by drug companies stems in part from the current politics of mental health – deaths have stemmed from rapid tranquillisation often by harassed staff in psychiatric units. Read more…

Dependence

Before considering this in detail, we must exclude a type of physical dependence that occurs with a great number of drugs and ordinarily is of little consequence. Many drugs will cause rebound symptoms once they are discontinued. This happens particularly if they block receptors. This blockade leads to the blocked receptors becoming hypersensitive. When the blocking drug is then removed, these receptors are flooded with the normal neurotransmitter and they respond vigorously. It may take 48-72 hours for them to settle back down to normal.

Examples of this are the rebound phenomena that may occur with beta-blockers, such as propranolol, and the cholinergic rebound that may happen after stopping antidepressants with marked anticholinergic effects. Propranolol rebound may lead to palpitations, sweating and flushing. Cholinergic rebound may produce poor sleep and nausea or vomiting. These syndromes are not serious, and high doses of the relevant compounds are stopped abruptly. Read more…

Barbiturates

Concerns about the over-prescription of benzodiazepines in recent years have led some prescribers to look at alternative hypnotic agents – either older compounds such as members of the barbiturate or chloral families, antidepressants, or neuroleptics with a sedative profile. There are a number of problems with such prescriptions as will become clear.

Chloral Compounds

Chloral compounds (see the table below) were first produced in 1869. Their sedative effects were quickly recognised, leading to their use as hypnotics among other things. A number of factors militated against their widespread use. One was the difficulty in making them in other than foul tasting liquid formats. The subsequent discovery of the barbiturates, just before the First World War, largely put paid to them. Before that, however, many patients admitted to mental hospitals were treated with chloral draughts and would appear to have done well. Read more…

Benzodiazepine Structure

What is the place for hypnotics in this scheme of things? Basically the same place that alcohol has occupied for centuries. Most of us every so often, if we are anxious, worked up or have a lot of things on our mind will have on occasion resorted to alcohol to knock ourselves out. This it doers effectively on an episodic basis. There are drawbacks to alcohol, however. One is that it may produce a rebound insomnia – it knocks you out but also wakes you up several hours later as the effects wear off. It may also wake you up to pass urine or because of dehydration.

Hypnotics do roughly the same thing, with similar benefits and side effects. Judiciously used, they are wonderful. Taken in the early stages of a problem they may abort the later development of habitual anxiety-based insomnia. Taken too regularly or chronically, they may produce their own problems.

The place for the hypnotics lies in the management of sleeplessness rather than in the management of insomnia. Where there is genuine sleeplessness stemming from jet lag or an underlying physical condition, or problems with falling asleep in what may be uncomfortable circumstances or situations of stress, a hypnotic may be of great benefit. The presumption in these cases is that there is a transient sleeplessness and the condition is being managed until normality returns. In certain circumstances, such as where a chronic physical condition regularly compromises sleep, it would seem that hypnotics can be used chronically without causing much in the lines of dependence or other problems. Under the side effects section below, problems such as the risks posed to driving from sedative effects of these drugs will be outlined but it should also be borne in mind that the fatigue consequent on sleeplessness is seen as a rather trivial issue. Read more…

Beta-blockers

In recent years, with concern over benzodiazepine use, there has been interest in the use of beta-blockers in the treatment of anxiety, principally propranolol (Inderal) and atenolol (Tenormin). Although they are used mainly in the treatment of hypertension, angina and cardiac arrhythmias, the rationale for their use in psychiatry is that they block the peripheral manifestations of anxiety, such as increased heart rate or shaking in the hands. Signs such as these are the cues we all use to judge, how anxious we are. When these effects of anxiety are controlled, it seems that two sets of feedback loops may be interrupted. Part of becoming anxious involves anxiety at signs of becoming anxious, such as increased heart rate and shaky hands. These manifestations of anxiety can lead to worries in their own right, for example, for the concert performer who may worry about both the audience and the effects of shaky hand on the violin bow. Similarly public speakers may have their nervousness faced with an audience augmented by nervousness about the effects of tremulous voice or a dry mouth on the act of speaking itself. Controlling effects such as heart rate, voice timbre and hand steadiness, therefore, can interrupt one feedback loop by taking away a set of stimuli to further anxiety. It can also interrupt another and ease the central anxiety by, as it were, removing the cues by which we all judge just how anxious we are. Read more…

5-HT Receptors and Drugs

The 1990s look like being the decade of the neurotransmitter 5-HT – otherwise called serotonin. This was first isolated in the intestine in 1933 and called enteramine. It was rediscovered in blood vessels in 1947 and found to cause them to constrict, which led to it being called serotonin. In 1949, it was established that the chemical structure of serotonin was 5-hydroxytryptamine or 5-HT for short. Both names, 5-HT and serotonin have remained in use. Serotonin survives partly because SmithKline Beecham stumbled on the marketing appeal of the acronym SSRI – selective serotonin reuptake inhibitor – as part of their marketing of paroxetine.

Serotonin was discovered in the brain in 1953. Shortly before in 1948, LSD had been discovered and it had been recognised that there were structural similarities between 5-HT and LSD. This led, at the beginning of the psychopharmacological era, to great interest in the role brain 5-HT might play in mental illness (1, 2, 3).

The initial biochemical observations on antidepressants were that these drugs had effects on the 5-HT system. But despite this, 5-HT more or less disappeared from view for over 20 years. One important reason for this was the emergence of the catecholamine hypothesis for depression. Although antidepressants affected both catecholamines and 5-HT, in 1965, Joseph Schildkraut proposed that the effects on catecholamines were more important. This led to a focusing of research on the catecholamine system and a virtual ignoring of the 5-HT system, at least in terms of depression (see All You Need To Know About Antidepressants). Read more…

To attempt to write an impartial account of the benzodiazepines is all but impossible (1,2). When they were first introduced these drugs (see the table below) were seen as being of major benefit, and they were widely regarded as extremely safe and demonstrably effective. They were popular with both physicians, consumers and the pharmaceutical industry. Indeed, they appeared to be so effective and so effective and so popular they have caused serious problems for the development and marketing of any new anxiolytic.

More recently, the benzodiazepines have been described as the greatest menace in peace time. They have been seen as the epitome of the psychotropic drug juggernaut, whose prescription must be curbed at all costs. There has been a variety of TV and radio programmes highlighting their dangers and the horrors of dependence, and it has been claimed that coming off them is harder than coming off heroin. But strangely enough, benzodiazepine dependence is perhaps the only case of drug dependence in which the dependent person is viewed with sympathy. Read more…