Addiction Treatment Blog

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.

The chloral compounds are now produced as capsules, although chloral draughts can still be made up. They are popular with some prescribers as they do not appear to give the buzz sometimes had from benzodiazepines and are, therefore, it seems less likely to be abused. For this reason they are used in some hospitals as the sedative of choice for illicit drug users. They are also popular with hospital pharmacies in that they cost pennies rather than pounds. In these days of general practitioners holding their own budgets, this may lead to their revival. A chloral prescription may cost the pharmacy as little as 5p per week.

Chloral compounds may, however, cause dependence, as well as gastric irritation, heartburn and rashes in some people. They are very hazardous in overdose, and are probably contra-indicated where there is co-existing disorders of almost any sort-cardiac, renal or gastric.

Barbiturates and related compounds

Until the mid-1960s the barbiturates, and related compounds such as glutethimide (see the table below), were the standard hypnotics. Concern about their dependence-producing potential, their dangers in overdose and the fact that these drugs interacted with a large number of other psychiatric drugs led to their abandonment with the emergence of the benzodiazepines.

The first barbiturate compounds were produced in the 1860s. In 1912, phenobarbitone was discovered and it became one of the first psychotropic drugs to be systematically marketed. Since then, there have been a great number of barbiturate compounds. They are widely used in anaesthesia and for the control of epilepsy – with far fewer complications than their fearsome reputation in psychiatry might suggest. Essentially the barbiturates and benzodiazepines both work on the same GABA receptor complex.

In an attempt to avoid problems of physical dependence on barbiturates and the concern about overdose, manufacturers introduced a series of compounds during the 1950s and 1960s, each with the claims that an effective and safe compound had finally been found. In reality, each new compound seemed to even more popular with consumers but for all the wrong reasons. The final cast of the die was methaqualone (Mandrax) – a most effective hypnotic but whose various benefits were immediately apparent to the underground drug subculture growing up in the 1960s.

It is rare to find any barbiturates prescribed ow as hypnotics. They have some use as general sedatives in states of acute agitation (see The Neuroleptics article). They combine well with neuroleptics in the short term, allowing lower doses of each to be used. They may also be used for abreactive purposes (see Benzodiazepine Anxiolytics article).

Their use as sedatives for the management of acute agitation is one thing but as chronic hypnotics is quite another. The barbiturates induce the liver enzymes that metabolise other drugs and accordingly the plasma levels of co-administered contraceptives, antibiotics, antidepressants, steroids, anti-asthmatic and anti-arrhytmic compounds may fall. If taken in overdose they are fatal, where the benzodiazepines and the more recently introduced agents are not. They are potent dependence-producing compounds and even the shorter-acting compounds of the groups listed above are liable to cause hangover effects the next day. Less commonly they may produce dissociative reactions, unsteadiness of gait, blurred or double vision and skin reactions especially periorbitally.

Chlormethiazole

Prescribed as Heminevrin, this is one of the most widely used hypnotics. It is also used to ameliorate alcohol withdrawal. It seems to be either loved or hated. It is liked by prescribers in that it works and does not produce hangover effects because of its short half-life. This makes it sustainable in the elderly for whom it is particularly marketed and used. It is also popular with consumers apparently because for a considerable proportion of takers its effects are distinctly pleasant. It has a considerable street value.

It is disliked by many psychopharmacologists because it is a drug that defies conventional classification. It is distrusted by some prescribers because it is over-liked and has a high dependence potential. In terms of side effects, it can also produce nasal congestion, nasal irritation and heartburn.

A note on heartburn and gastric irritation

In recent years, there has been a trend among doctors to prescribe any hypnotic other than a benzodiazepine, owing to the fear of being sued for creating dependence. This tendency ignores the fact that the benzodiazepines came to prominence because they were much safer than older compounds. In particular, they are less likely to cause problems such as heartburn. In recent years, it has come increasingly common to find people taking hypnotics, such as chloral hydrate or chloral betaine, who have also been put on ranitidine (Zantac), cimetidine (Tagamet) or omeprazole (Losec) by their physicians, for heartburn or ulcers. These are very expensive tablets, more so than most new psychiatric drugs, which seems rather self-defeating. They also have side effects in their own right.

Others

Given current levels of concern about both benzodiazepines and barbiturates, as well as hypnotics and anxiolytics in general, a number of clinicians prefer to prescribe sedative antidepressant (especially trimipramine) or neuroleptic (chlorpromazine or thioridazine). Although these work, one may wonder at the advisability of this approach. If handled properly, it is almost certainly better to prescribe a conventional hypnotic. Current recommendations for proper handling suggest prescribing hypnotic for no more than a week per month. If there is a chronic problem, then prescription every 3rd or 4th night may be an option to produce intermittent sleep and break the cycle of fear of insomnia.

In contrast, antidepressants and inparticular the older, more sedative ones, can be fatal in overdose and produce more in the line of side effects (see Side Effects of Antidepressants article). The sedative neuroleptics are only sedative for some, and they too produce side effects, a number of which may be very worrying if the person affected is unaware of what to expect. If prescriptions of such compounds are made without the taker being briefed as to the possible emergence of tardive dyskinesia or other problems, it could be argued that prescribers are on very shaky grounds.

There are two more recently developed antidepressants which are being used increasingly for hypnotic purposes. These are trazodone and mianserin (see The Management of Side Effects and 5-HT Receptors and Drugs articles). Both of these are 5-HT-2 receptor antagonists. The significance of this is that the 5-HT system is involved in the generation of what is termed slow-wave sleep, and acting on this system leads to both of these compounds being more reliably sedative than other antidepressants or neuroleptics. Again, however, although safer in overdose, one has to question the use of such compounds for the management of acute sleeplessness. In the case of EEG evidence of deficient stage-4 or stage-3 sleep, the picture may be quite different and such compounds may be quite appropriate. For the management of insomnia, the calculations of possible benefits and drawbacks becomes complex.

Finally, there are antihistamines, of which Phenergan and Vallergan are the most commonly prescribed. These are used in the main for children. They often ‘work’, although their use arguable should be discouraged for this purpose as they may have marked hangover effects on the child the next day, which may potentially lead to accidents and/or poor performance at school.