The history of psychopharmacology is full of curiosities and discoveries of various kinds.

Some of these discoveries are the result of arduous research and others are derived from the observation of effects in the treatment of other disorders (such as tuberculosis or asthma). Over time, research has allowed the creation and consumption of substances that effectively help us to treat multiple psychological problems. This is the case of benzodiazepines, one of the most well known types of psychotropic drugs in the treatment of anxiety .

Benzodiazepines: what are they?

Benzodiazepines are a group of psychopharmaceuticals with a mainly anxiolytic effect whose discovery was a great revolution in the treatment of anxiety. Born at a time when barbiturates were indisputably the treatment of choice for anxiety-type problems despite the high risk of overdose and dependence, their high level of success in reducing symptoms with much lower risks and side effects quickly made them the most widely consumed type of psychoactive drug.

These are relaxing substances with a large number of clinical applications, despite the fact that like all psychopharmaceuticals presents a series of risks and side effects to be taken into account when applying them. They are usually administered orally, although in cases where rapid action is required, intravenous administration (which is much quicker) may be recommended.

The mechanism of action of benzodiazepines is based on their action as an indirect agonist of GABA or gamma-aminobutyric acid, a neurotransmitter that allows the correct management and not overloading of the brain by reducing and hindering the transmission of nerve impulses. Specifically, benzodiazepines cause GABA to exert a greater influence on the system, which, being an inhibitor-type neurotransmitter, produces a depressing effect on the nervous system. Since the limbic system has a large number of gabaergic receptors, the impact of benzodiazepines on anxious processes and moods is very high. Thus, the level of activation of the organism decreases, producing a relief of the anxious symptomatology together with other effects such as muscular relaxation and sedation.

Types according to their half-life

There are different types of substances that belong to the group of benzodiazepines . Although they could be grouped in different ways, one of the most common classifications is that which takes into account the half-life of the drug in the body, i.e. the time it remains active within the body.

Thus we can find three major groups of benzodiazepines, whose characteristics will make them more suitable for one or another situation.

1. Short life/short action benzodiazepines

These are substances that remain in the body for a short time (less than 12 hours), and are not suitable for treating long-term anxiety disorders. However, are the fastest acting benzodiazepines , which are a great help in combating the appearance of sudden anxiety symptoms such as anxiety attacks or problems that only require a momentary relaxation, such as difficulties in falling asleep.

The main problem for this subgroup is that if the effects wear off quickly, if they are to be maintained, use of the substance will become more common, and dependence is likely to develop. In addition, they tend to cause a higher level of side effects. Some drugs in this group are triazolam or midazolam.

2. Long life/long action benzodiazepines

This type of benzodiazepine has the great advantage that stays in the body for a long time , being helpful in anxiety disorders. In contrast, the fact that they remain in the body so long means that the effects of the doses can build up, which could have undesirable sedative effects.

In addition, they take some time to take effect, so they are not suitable when an immediate response is needed. They can remain and act for more than thirty hours after consumption. Within this group is the best known anxiolytic, diazepam, along with others such as clonazepam.

3. Lifetime benzodiazepines/intermediate action

Somewhere between the two previous types , the intermediate-lived benzodiazepines show early (although not as immediate as short-acting) action over a relatively long period of time. They last between twelve and twenty-four hours. Alprazolam or loracepam are some of the drugs in this group.

Multipurpose drugs: indications

As noted above, benzodiazepines have a number of uses. Some of the main problems in which these drugs are used are as follows.

1. Anxiety disorders and episodes

The application for which benzodiazepines are best known, having been the drug of choice for many years for this type of problem (they have now been dethroned as the treatment of choice in multiple disorders). The type of benzodiazepine to be used in each type of disorder will depend on the characteristics of the disorder .

For example, if rapid action is needed in response to the emergence of an anxiety attack, a short-lived benzodiazepine can be applied. In the presence of phobias with a high likelihood of occurrence of the phobic stimulus (such as social phobia), long or half-life benzodiazepines such as alprazolam may be used. In disorders such as generalised anxiety disorder or panic disorder, clonazepam, a long-acting version, tends to be one of the most effective.

2. Insomnia

One of the properties of benzodiazepines, which is sometimes an unwanted side effect, is their sedative potential . This is why they are useful in combating sleep problems.

Short-lived benzodiazepines such as triazolam are often used when difficulty is in reconciling sleep, but some long-lived drugs such as fluracepam are also used if the problem is in frequent waking or maintenance of sleep.

3. Mood disorders

Although in both depression and bipolar disorder there are other drugs that are prioritized over benzodiazepines, in some cases alprazolam or clonazepam are used because they can calm the patient and reduce anxiety.

4. Seizures, spasms and motor agitation

Seizures of the epileptic type appear when one or several groups of neurons become hypersensitive and are easily excited. As noted above, the main mechanism of action of benzodiazepines is the potentiation of GABA as an inhibitor of neuronal excitation, so by enhancing depression of the nervous system benzodiazepines are useful in controlling seizures.

Other motor-type symptoms can also be mitigated due to the effect as a muscle relaxant and sedative.

5. Alcohol withdrawal syndrome

Abrupt cessation of alcohol consumption in subjects who have developed tolerance and dependence may produce withdrawal syndromes, whose symptoms may include anxiety, coordination problems and agitation. Both at hospital and outpatient level, the use of benzodiazepines allows these symptoms to be controlled , taking advantage of their sedative activity to reduce their intensity.

Risks and associated side effects

The use and administration of benzodiazepines have multiple advantages in a wide range of disorders. However, their use is not without risk, possessing different characteristics that cause their dose and time of use to be regulated.

1. Addiction

One of the main problems of this type of drugs is its addictive potential . Although compared to their predecessors, benzodiazepines are much less addictive, they are substances whose prolonged use can produce tolerance, dependence and even withdrawal syndromes.

In this respect, the longer the half-life in the body, the less consumption will be necessary to maintain its effects, so that in general the long-lived benzodiazepines are the least addictive. The correct dosage of benzodiazepines and the time they are to be consumed is necessary to avoid such problems.

2. Abuse and overdose

An overdose of these substances usually produces an exacerbation of the effects , causing a deep depression of the nervous system. It does not usually have fatal repercussions unless the patient is very old and/or has concomitant medical problems.

3. Withdrawal syndrome

In terms of withdrawal syndromes, it is common for symptoms to appear that are the opposite of those produced by the drugs, a rebound effect in which the presence of insomnia, headaches, anxiety , cramps and even convulsions stand out. To avoid this, it is necessary to schedule its withdrawal with extreme caution.

4. Sedation, decline in concentration and performance

The sedation they produce is another problem that the use of benzodiazepines can cause . Although in many cases they are used precisely to relax and facilitate sleep, on occasions when the only aim is to reduce anxiety, this effect can be harmful because it reduces motor skills, concentration and the effectiveness of the subject in carrying out tasks.

5. Memory problems

The consumption of benzodiazepines can cause, especially when they are first administered, memory problems . The type of problems they cause are usually difficulty in acquiring and consolidating new information, as well as in remembering previous information.

6. Paradoxical reaction

In some cases, and especially with the elderly, the use of benzodiazepines may have the opposite effect to that expected. In these cases, it increases the excitement of the nervous system, causing both cognitive and motor distress and agitation .

Bibliographic references:

  • Gómez, M. (2012). Psychobiology. Manual CEDE de Preparación PIR.12. CEDE: Madrid
  • Salazar, M.; Peralta, C.; Pastor, J. (2011). Manual of Psychopharmacology. Madrid, Editorial Médica Panamericana.
  • Stevens, J.C. & Pollack, M.H. (2005). Benzodiazepines in clinical practice: consideration of their long-term use and alternative agents. J Clin Psychiatry; 66 (Suppl 2):21-7.