Anti-anxiety medicines

Anxiolytics are widely prescribed in primary and secondary mental health services despite the NICE guidelines highlighting that the preferred treatments for anxiety are psychosocial treatment or self-help approaches based on CBT principles. In clinical practice, drug interventions are often necessary due to the diffi culties accessing psychosocial treatments. Where medication is prescribed NICE recommend that the first-line treatment should be an SSRI antidepressant. If benzodiazepines are to be used they should be prescribed for a limited period (2–4 weeks) and that they should be used for emergency management only (not for obsessive compulsive disorder (OCD) or post-traumatic stress disorder (PTSD)).

When attempting to manage anxiety it is always worth considering if it is associated with a co-morbid mental health problem, for example drug/alcohol use, depression or psychosis. The recommended drug treatment for anxiety disorders depends upon which type of anxiety is diagnosed. Anxiety disorders can be classed under the following groups: generalised anxiety disorder (GAD), panic disorder, social phobia, OCD and PTSD.

Antidepressants

The issues surrounding antidepressants have already been discussed and we refer the reader to the previous section in terms of side effects and interactions. If prescribed an SSRI, the service user should be informed that there is a possibility of anxiety symptoms becoming more pronounced before the therapeutic effect is achieved. The mechanism of action of antidepressants in anxiety management is as equally baffl  ing as the mechanism of action for depression and, owing to the delayed onset of therapeutic action, these drugs have no place in the acute management of anxiety. The mechanism of action could be related to the complex relationship between changes in neurotransmission of serotonin, noradrenaline, dopamine and some GABA receptors.

Benzodiazepines

Benzodiazepines (BDZs) (e.g. diazepam, lorazepam, clonazepam) are widely prescribed for a variety of stress-related illnesses. However, their use is sometimes unjustified. They are also sometimes used for insomnia, alcohol withdrawal management, muscle relaxation, emergency seizure control and rapid tranquilisation.

Mechanism of action

The way BDZs work is more fully understood than most psychotropic drugs. Throughout the central nervous system (CNS) a naturally occurring transmitter molecule called GABA exists, which inhibits neuronal activity. Benzodiazepines potentiate the action of GABA by binding at receptor sites of neurones. Chloride (Cl–) ion channels in the neurone open when bound with GABA, allowing the influx of Cl– ions from the surrounding extracellular fl uid. This infl  ux makes the neurone incapable of accepting more Cl– ions and, as long as the channel remains open, insensitive to further stimulation. This insensitivity is what is responsible for the inhibiting effect of GABA, which is increased when BDZs are taken. All true BDZs act on GABAa receptors to exert their inhibitory effect. The main differences between them are the variations in half-lives. The length of half-lives is clinically relevant as this will infl uence how long the drug takes to work and for how long the effects will be apparent. It also relates to how likely a drug is to cause withdrawal effects, and its propensity for misuse as a recreational drug.

Side effects and interactions

If BDZs are not taken with other CNS depressants then they are relatively safe in overdose. If respiratory depression does occur then fl  umazenil can be given to reverse the effects. Flumazenil is a BDZ antagonist and should be available in clinical settings where large or injected doses of BDZs are a possibility. The common side effects of BDZs include sedation/somnolence, headaches, confusion, ataxia (unsteadiness on feet), blurred vision, gastrointestinal problems, jaundice, amnesia and paradoxical excitement. The likelihood of paradoxical excitement and behavioural disinhibition increases where someone has pre-existing tendencies for being aggressive, has a learning disability, is young or has a diagnosis of personality disorder. The most serious interaction of BDZs is with other CNS depressants such as alcohol, methadone or opiates, causing a risk of respiratory depression. Benzodiazepines are metabolised by P450 liver enzymes but they do not increase or decrease the action of these enzymes and, as such, will not infl  uence plasma levels of other drugs. It is possible that plasma levels of BDZs can be influenced by co-administration of some other drugs.

Caution is advised when using BDZs in the older population as older people are more susceptible to adverse effects and falls.

Tolerance and addiction

It is widely accepted that prolonged use of BDZs (over 4 weeks) is associated with physical and psychological tolerance, and addiction. The anti-anxiety and sleep-inducing properties of BDZs reduce with longer term use. As a result, greater doses of the drug are needed to exert the same effects. This is why BDZs should only be used for short periods. The chances of addiction are reduced if the drug is used for less than 4 weeks, a BDZ with a longer half-life is used or if they are taken intermittently rather than daily.

The mechanism of action of withdrawal relates to the reduced action of GABA and the subsequent rebound stimulation of the CNS. The symptoms of withdrawal are both physical and psychological. Both groups of withdrawal symptoms can mimic some mental health problems and because of this service users may misinterpret withdrawal to be a sign of relapse. The common withdrawal symptoms include stiffness, weakness, intestinal problems, fl u symptoms, visual disturbances, possible seizures, anxiety, insomnia, vivid dreams, cognitive impairment, depression and delusions/hallucinations. Benzodiazepines with shorter half-lives will induce withdrawal symptoms earlier and in a more severe form. The Maudsley Prescribing Guidelines provide excellent recommendations for managing BDZs withdrawal, with the initial management being to swap any shorter acting drugs to diazepam (which has a longer half-life of 20–40 h).

Other anti-anxiety medicines

Other drugs are used for the management of anxiety and any related sleep problems; the choice of drug depends on the anxiety disorder diagnosed.

The use of barbiturates to manage acute anxiety is generally avoided in clinical practice due to the possible toxic effects in overdose, which can lead to coma and death. Overdose of barbiturates can occur accidentally due the small differences between therapeutic doses and toxic doses. Barbiturates act on the same receptors to potentiate GABA as BDZs.

Buspirone is a non-benzodiazepine anxiolytic. Its mechanism of action is different to that of BDZs as it does not act on GABA receptors but exactly how it works is unclear. It appears that its therapeutic effects are related to its action on (and the relationship between) dopamine, serotonin, noradrenaline and acetylcholine. It takes around 3–6 weeks to work and therefore has no place in the acute management of anxiety. Buspirone does not appear to cause dependence and has no clinical sedative or anti-convulsant properties. Its side effects include dizziness, drowsiness, headache, insomnia, nausea, dry mouth and palpitations. Hypertensive crisis can be a consequence of taking buspirone and MAOIs, and serum levels of buspirone can be increased to toxic levels if taken with some drugs that inhibit some P450 liver enzymes (e.g. erythromycin and nefazadone).

Non-benzodiazepine hypnotics such as zopiclone and zolpidem are used to manage insomnia. However, they cause side effects similar to those of BDZs and should be used sparingly. In fact they really have no place in the treatment of anxiety disorders and are licensed only to promote sleep. Some antihistamines (e.g. promethazine) are occasionally used for their sedative properties. They work by blocking histamine H1 receptors but again they are not licensed for use in anxiety disorders.

Beta-blockers (e.g. propranalol) are sometimes used to alleviate some of the physical manifestations of anxiety. They can help to reduce tremor and palpitations but will have no direct effect on tension or sleep problems. When noradrenaline is released across a synapse it binds with a variety of receptors including beta1 and beta2. Noradrenaline acts at these receptors to increase heart rate/force and increase contraction of skeletal muscles. By blocking the action at the beta receptors the effects of noradrenaline are reduced and hence the reduction in heart rate and tremor. Non-specifi  c beta-blockers like propranalol block beta1 and beta2 receptors, which results in constriction of the bronchioles and therefore should never be given to a service user with asthma or other respiratory problems.

Key points regarding anti-anxiety medicines:

• The most effective treatment to promote recovery from anxiety disorders is CBT based.
• If medication is to be used it should be an SSRI in the fi  rst instance.
• Benzodiazepines are helpful to manage acute symptoms, but they are addictive and should only be used short term or on a PRN bas
is.
• Anxiety can be a symptom of many mental health problems; the underlying condition should be addressed to promote recovery.