Insomnia from antidepressants

The antidepressant mirtazapine is pharmacologically similar to mianserin. It has a slightly weaker blocking action at i-adrenoceptors, and this is claimed to give it a dual mode of action, increasing the release of both noradrenaline and serotonin (1). It is claimed to have a more rapid onset of action than some SSRIs, but this may be due to its prominent sedative effect, which improves insomnia from the start of treatment. 

Saint-John s-wort was used in ancient Greece and medieval Europe, where it was believed to ward off evil spirits. Its name derives from wort, the Old English word for herb, and the fact that it was harvested in Europe on the eve of St. John s day (June 24th) and burned to purify the air (Fleiligenstein and Guenther 1998). Traditional uses include treatment of depression, insomnia, enuresis, and anxiety. Modern use has focused on its antidepressant effects and possible antiviral effects for treatment of the human immunodeficiency virus (FIIV) (Fleiligenstein et al. 1998) (table 7.3). There has been some interest in its antiglioma effects as well (Couldwell et al. 1993). 

Medications that enhance norepinephrine activity are used to treat depression and ADHD. Boosting norepinephrine can also produce numerous side effects including nervousness and anxiety, insomnia, and loss of appetite. With mirtazapine and the TCAs, these side effects are usually not a problem because these antidepressants also block histamine receptors. Their antihistamine effects promote increased appetite and drowsiness that tend to offset the side effects that might be experienced from increased norepinephrine activity. 

There have been three randomized clinical trials and multiple case reports and open-label trials with the tricyclic antidepressants (TCAs) in PTSD, although only one study of childhood PTSD (Southwick et al., 1994) has been reported. Robert et al. (1999) reported the use of low-dose imipramine (1 mg/kg) to treat symptoms of ASD in children with burn injuries. In this study, 25 children ages 2 to 19 years were randomized to receive either chloral hydrate or imipramine for 7 days. Ten of 12 subjects receiving imipramine experienced from half to full remission of ASD symptoms, whereas 5 of 13 subjects responded to chloral hydrate. Sleep-related flashbacks and insomnia appeared to be particularly responsive to treatment. 

In patients receiving antidepressants for acute major depression, the initial therapeutic response is often delayed by several weeks. Patients with severe anxiety or insomnia may benefit from the concurrent, time-limited use of a benzodiazepine or short-acting hypnotic (Chapter 3). A patient may initially experience a return of energy and motivation while still having feelings of hopelessness and excessive guilt. Such patients may be at an increased risk for suicide because a return of energy in an extremely dysphoric individual may provide the impetus and means for an act of self-destruction. 

At the present time, the TCAs are used primarily in depression that is unresponsive to more commonly used antidepressants such as the SSRIs or SNRIs. Their loss of popularity stems in large part from relatively poorer tolerability compared with newer agents, to difficulty of use, and to lethality in overdose. Other uses for TCAs include the treatment of pain conditions, enuresis, and insomnia. 

Further disruption of REM sleep is related to the presence of hallucinations and REM sleep behavior disorder in Parkinson s patients. A decrease in REM sleep has been associated with nocturnal hallucinations (125), and REM intrusion during daytime hallucinations has been reported (126). More than one third of Parkinson s patients also suffer from REM sleep behavior disorder (RBD) (127,128) or REM sleep without atonia (128). In these patients, there is also a significant reduction in total sleep time. In many cases RBD is diagnosed several years prior to the onset of Parkinson s disease (129), although a link between disease severity and duration and the presence of RBD has also been reported (128). RBD is most often treated with the administration of clonazepam (104,129). Patients with comorbid dementia and depression also experience a high level of sleep disturbance, associated with nocturnal vocalizations and hallucinations (130). One side effect of many antidepressant medications, however, is insomnia and sleep disturbance (131). 

A range of medications is available to treat insomnia, ranging from herbal preparations such as valerian to the recently introduced z compounds, zopiclone, zolpidem and zaleplon. Many drugs used for other primary purposes have sedative and sleep-inducing properties as side effects these include many tricyclic antidepressants and antihistamines. 

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