Sedatives and Hypnotics

Sedatives and Hypnotics

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A sedative is meant to calm combative or over-active patients or reduce the impact of impending stress. A hypnotic is primarily meant to promote sleep. How do these medications actually work?

There is some overlap in both the terms and the drugs used in this category. Primarily, a sedative is meant to calm combative or over-active patients or reduce the impact of impending stress (such as in pre-operative sedation). A hypnotic is primarily meant to promote sleep.

The overlap occurs because some of the same drugs at different dosages can be used for either purpose.  One example of this is benzodiazepines.

Benzodiazepines

Benzodiazepines have been manufactured since the 1960s (chlordiazepoxide, diazepam) and more than 50 different types are available in the US. With so much competition, manufacturers have been hard pressed to distinguish the benefits of their product over others. Whether a particular benzodiazepine is used for sedation or as a hypnotic depends on the time to onset, the half-life of the parent drug (and its active metabolites) and the side effects profile.

The quicker a particular benzodiazepine acts and the shorter the half life, the more useful it is as a hypnotic. This is because patients can predict the onset of somnolence and their body can clear the medication by the next day. Unfortunately, these two factors increase addiction potential. While all benzodiazepines are both physically and psychologically addictive, those used as hypnotics have the most risk.

The mechanism of action for benzodiazepines is not completely understood. They are GABA agonists, which mean they potentiate the naturally occurring neurotransmitter GABA (gama aminobutyric acid) which has inhibitory properties in the brain. Just exactly how this reduces anxiety and promotes sedation remains under study. The peripheral effects make benzodiazepines useful as muscle relaxants and in the treatment of acute myoclonic or epileptic seizures.  They also find use mixed with anti-psychotics (haloperidol plus lorazepam) and given as an injection for psychiatric emergencies in patients that require restraints.

One of the most interesting applications is as an amnesia inducing agent. Benzodiazepines given before surgery can both relax the patient and cause them to forget the subsequent procedure. Diazepam given intra-venously is used in dental surgeries which require patients to be awake (to some extent) without suffering the anxiety of the procedure. They serve as ‘date rape’ drugs for the same reason. Flunitrazepam (Rohypnol) has an onset of about 45 minutes and causes anteretrograde amnesia. This produces a victim who is malleable and leaves them without a clear memory of the crime.

Classic Sedatives and Hypnotics

The most ancient sedative/hypnotic is probably ethanol, closely followed by opium. Potassium Bromide was given as a sedative in the 19th century as well as chloral hydrate. The barbiturates became available in the early 20thand replaced most of the earlier drugs. In modern times, barbiturates still find use as hypnotics, although benzodiazepines are considered a much safer alternative.

Agents such as antihistamines and melatonin are also available and many patients will self treat with these non-prescription alternatives before seeking help for insomnia.

Insomnia

It is estimated that about 10% of the US adult population suffers from chronic or severe insomnia, however, about half of this is attributable to medical conditions (i.e. sleep apnea secondary to obesity) and do not have a primary psychological cause. This makes a thorough medical examination necessary before considering the available medications. Attention must also be paid to current medications and temporary stressors, both of which may lead to insomnia.

The assumption that depression causes insomnia needs comment. Depression and insomnia are associated (a diagnosis of primary insomnia does increase the risk for a future diagnosis of depression or anxiety). However, they should be viewed as co-morbid conditions, rather than one causing the other.

Insomnia often results from some precipitating event, and about 70% of patients with primary insomnia can identify a reasonable cause. Prolonging or reinforcing comes when worries about sleep (and the consequences of insomnia) perpetuates the condition. Cognitive and behavior treatment (either with or without medication) is needed to improve ‘sleep hygiene’ and teach patients useful techniques. Often, for example, patients may take daytime naps in the hopes of ‘catching up’ which actually aggravates the problem.

Cognitive behavior therapy (CBT) has been shown to help many patients (50 -70% of patients show improvement) and is comparable to benzodiazepines in efficacy. More importantly, most patients will maintain improvement at 6 months after a course of CBT – while removal of a drug precipitates reoccurrence.

Patients who are not helped by therapy alone will require a sleep aid. Ideally, the choice of agent will depend on the results of a sleep study which measures not only the duration, but the quality of sleep prior to treatment. Sleep clinics monitor patients with an EKG to discover depth and duration of various stages of sleep. Information about a specific patient can determine if the problem is onset, duration or depth of sleep. Generally, patients will be asked to keep a sleep diary for several weeks as an aid in diagnosis.

All hypnotics help a patient get to sleep, but most will not keep them sleeping throughout the entire night. Hypnotics find the most use in temporary insomnia, where some life adjustment is occurring – the death of a loved one, for example.

It should be emphasized that hypnotics are not a long-term solution for sleep disturbances. Patients should be discouraged from using them every night and re-evaluation is needed on a regular basis. None of the drugs marketed as hypnotics (with the possible exception of zolpidem – a non-benzodiazepine) are meant for chronic use (more than 3-4 weeks). Therapists are often pressured by patients into extending the duration of drug treatment and will have to be forthright in asserting that hypnotics are not a solution. In fact, some studies suggest that longer term usage actually exacerbates primary insomnia.

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