Sedation with antidepressants

Despite widespread use of standard hypnotics and sedating antidepressants for chronic insomnia, their role for this indication still needs to be defined by further research [8], In particular, clinicians must be cautious with antidepressants, which disturb sleep architecture and have various side effects [54, 55],... 

Trimipramine is a sedating tricyclic antidepressant that has been used as a hypnotic (1) it shares this activity with other drugs of its class, notably amitriptyline, dosulepin, doxepin, and trazodone, and with the tetracyclics mianserin and mirtazapine. Trimipramine may be preferred for this purpose, since it has less effect on sleep architecture, including REM sleep (2), and has only a modest propensity to produce rebound insomnia in a subset of patients (3). Sedative antidepressants may be particularly appropriate for individuals at risk of benzodiazepine abuse and patients with chronic pain (4). The usual pattern of tricyclic adverse effects, especially antimuscarinic and hypotensive effects and weight gain, can be expected. Some authors, enthusiastic about GABA enhancers, contend that antidepressants are not useful hypnotic alternatives (5). 

Antidepressant medications are designed to counteract these symptoms. However, when alcohol, itself a depressant, is combined with antidepressant medications, serious consequences can result. For example, some antidepressants cause sedation and drowsiness. Alcohol has similar effects, and the combination of the two could easily cause a person to fall asleep while driving. Initially, alcohol might seem to improve the mood of a depressed person, but its overall effect is often to ino-ease the depression symptoms. 

Trazodone routinely causes sedation, which is why it is used far more often as an adjunct with other antidepressants for sleep than as a primary agent for the treatment of depression. Priapism is a rare but serious adverse effect in males who take trazodone. In addition, orthostatic hypotension and dizziness are more common with trazodone than with nefazodone because the latter agent has a weaker effect at a-adrenergic receptors and also has a balancing of adrenergic effects owing... 

The sleep-inducing effect of some antidepressants has been used as an additive strategy in depressed patients with complaints of insomnia to negate the side effects of BZDs that could be confused with worsening depressive symptoms, including asthenia, diurnal sedation, and concentration and memory problems. 

The most commonly used therapies for anxiety and depression are selective serotonin reuptake inhibitors (SSRIs) and the more recently developed serotonin noradrenaline reuptake inhibitors (SNRIs). SSRIs, which constitute 60% of the worldwide antidepressant and antianxiety market, are frequently associated with sexual dysfunction, appetite disturbances and sleep disorders. Because SSRIs and SNRIs increase 5-HT levels in the brain, they can indirectly stimulate all 14 serotonergic receptor subtypes [2,3], some of which are believed to lead to adverse side effects associated with these drugs. Common drugs for short-term relief of GAD are benzodiazepines. These sedating agents are controlled substances with addictive properties and can be lethal when used in combination with alcohol. The use of benzodiazepines is associated with addiction, dependency and cognitive impairment. 

One particular variant of the post-TBl behavioral disturbances, nighttime agitation, can be managed successfully with low bedtime doses of sedating antidepressants such as trazodone (25-50mg) or nortriptyline (10mg). These antidepressants may calm the patient and help him/her to sleep while avoiding the potential for confusion or disinhibition posed by other commonly used sleep medicines. 

What Is a Side Effect This chapter picks up where Chapters 1 and 2 left off. As we discussed in the earlier chapters, all medications, psychiatric and otherwise, have multiple effects. One takes a medication to achieve a therapeutic effect. Occasionally, a single medication may have more than one therapeutic effect. All other effects are side effects. Different medications may have differing therapeutic and side effects depending on the intended use. For example, trazodone and quetiapine are often prescribed to aid in sleep, and in this instance sedation is the desired effect, yet when used as an antidepressant and antipsychotic, respectively, the sedation is often an unwanted effect. Psychotropic medications typically have multiple effects. First, they usually interact with more than one nerve cell protein, be it a transporter or a receptor. Quite often, one of the medication s receptor or transporter interactions produces the therapeutic effect. The other interactions tend to not be involved in the therapeutic effect and only serve to produce side effects. Sometimes a neurotransmitter will have multiple different receptor types, but the medication interacts with... 

Imipramine is a tricyclic antidepressant and when it is administered concomitantly with alcohol, increased sedation occurs. 

Seizures The use of flumazenil has been associated with the occurrence of seizures. These are most frequent in patients who have been on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic antidepressant overdose. Individualize the dosage of flumazenil and be prepared to manage seizures. 

Some selective serotonin re-uptake inhibitors are powerful inhibitors of cytochrome P450 enzymes and the metabolism of e.g. tricyclic antidepressants can be inhibited resulting in serious toxicity. Additive sedation can be expected when given in combination with CNS depressants such as benzodiazepines but also with alcohol. Selective serotonin re-uptake inhibitors should not be used in combination with monoamine oxidase inhibitors as fatal reactions have been reported. 

This group includes compounds with actions on a range of neurotransmitter systems. Their antidepressant efficacy is mediated by reuptake inhibition of serotonin and noradrenaline, although side-effects such as sedation may also be useful. Their use in anxiety disorders is supported by a long history of clinical experience and a reasonable evidence base from controlled trials. Studies support the use of clomipramine (a potent serotonin reuptake inhibitor) in panic disorder and OCD (Lecrubier et al. 1997 Clomipramine Collaborative Study Group 1991), of imipramine in panic disorder and GAD (Cross-National Collaborative Panic Study 1992 Rickels et al. 1993), and of amitriptyline in PTSD (Davidson et al. 1993a). No controlled studies support the use of TCAs in social anxiety disorder. 

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