Sedation SSRIs

SSRIs Citalopram 10-30 mg fluoxetine 10-20 mg fluvoxamine 50 mg paroxetine 10-30 sertraline 25-150 mg all agents are given by mouth daily and can be dosed continuously or during the luteal phase only26 Sexual dysfunction (reduced libido, anorgasmia), insomnia sedation, hypersomnia, nausea, diarrhea... 

Common side effects of the SSRIs are somnolence, nausea, ejaculation disorders, decreased libido, dry mouth, insomnia, and fatigue. Tricyclic antidepressants (TCAs) commonly cause sedation, orthostatic hypotension, anticholinergic effects, and weight gain. TCAs are very toxic on overdose. 

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. 

Buspirone does not share any of the problematic benzodiazepine properties such as sedation, motor impairment, addiction, physical dependence, or withdrawal. The most common side effects of buspirone include dizziness, nausea, headache, fatigue, and dry mouth. Despite its activity in the serotonin system, buspirone is not associated with the sexual side effects that plague the SSRIs, SNRIs, MAOIs, and TCAs. 

Sertraline is a recent antidepressant that is called a selective serotonin reuptake inhibitor (SSRI). It is chemically unrelated to the older tricyclic antidepressants (see Section 5.3). It works by preventing the movement of the neurohormone serotonin into nerve endings. It can help to improve mood and mental alertness, increase physical activity, and improve sleep patterns. It is prescribed for obsessive-compulsive disorder and obesity. It may offer some advantage over fluoxetine by exhibiting little central nervous system (CNS) action. It has less sedation and anxiety and is shorter acting. 

Uses Acute migraine Action S otonin 5-HTi rec tor antagonist Dose 1—2.5 mg PO once r eat PRN in 4 h 5 mg/24 h max -1- in mild renal/hepatic insuff, take w/ fluids Caution [C, M] Contra Sev e renal/hepatic impair, avoid w/ angina, ischemic heart Dz, uncontrolled HTN, cerebrovascular synds, CTgot use Disp Tabs SE Dizziness, sedation, GI upset, paresthesias, ECG changes, coronary vasospasm, arrhythmias Interactions T Effects W/ MAOIs, SSRIs T effects OF CTgot drugs X effects W7 nicotine EMS May T PR or CyT int val, monitor ECG OD May cause profound HTN and cardiac ischemia symptomatic and supportive... 

Quazepam (Doral) [C IV] [Sedative/Hypnotic/ Benzodiazepine] Uses Insomnia Action Benzodiazepine Dose 7.5-15 mg PO hs PRN i in elderly hqjatic failure Caution [X, /-] NA glaucoma Contra PRG, sleep apnea Disp Tabs SE Sedation, hangovCT, somnolence, resp depression Interactions T Effects W/ azole antifungals, cimetidine, digoxin, disulfiram, INH, levodopa, macrolides, neuroleptics, phenytoin, quinolones, SSRIs, verapamil, grapefruit juice, EtOH effects W/carbamazepine, rifampin, rifabutin, tobacco EMS Use caution w/ other benzodiazepines, antihistamines, opioids and verapamil, can T CNS depression concurrent EtOH and grapefruit juice use T CNS depression OD May cause profound CNS depression, confusion, bradycardia, hypotension, and altered reflexes flumazenil can be used as antidote activated charcoal may be effective... 

With initiation of therapy with an SSRI, some patients describe anxiety or agitation. This can usually be overcome by reducing the dose and titrating upward more slowly. Insomnia can be a persistent activating side effect that can limit therapy or require the addition of a sedating agent at bedtime. Nausea and loose stools... 

Sleep. All of the SSRIs can potentially alter sleep architecture and decrease sleep efficiency, which may manifest itself as daytime sedation or trouble concentrating. The SSRIs may have differing effects on sleep. Fluoxetine has been reported to increase rapid eye movement (REM) latency, increase the number of awakenings, decrease sleep efficiency, and suppress... 

The introduction of SSRIs has raised the question regarding the comparative efficacy of CMI versus that of the SSRIs. SSRIs are important alternatives to CMI, because their range of side effects is clearly different [e.g., lacking anticholinergic side effects, sedation, weight gain]. Although SSRIs may provoke nausea, headaches, and sleep disturbances, these side effects are usually less troublesome to most patients. 

The side-effect profile of venlafaxine is similar to that of SSRIs and includes gastrointestinal symptoms, sexual dysfunction, and transient discontinuation symptoms. Like the SSRIs, venlafaxine does not affect cardiac conduction or lower the seizure threshold. In most patients, venlafaxine is not associated with sedation or weight gain. Side effects that differ from those of SSRIs are hypothesized to be related to the increased noradrenergic activity of this drug at higher doses these side effects are dose-dependent anxiety (in some patients) and dose-dependent hypertension. 

Treatment of GAD can be undertaken using a number of pharmacological agents. Benzodiazepines have been found to be superior to placebo in several studies and all benzodiazepines appear to be equally effective. However, side effects include sedation, psvchomotor impairment, amnesia and tolerance (Chapter 1). Recent clinical data indicate that SSRIs and SNRIs are effective in the treatment of acute GAD symptoms. Venlafaxine, paroxetine and imipramine have been shown to be effective antianxiety medications in placebo-controlled studies. Case studies also indicate the usefulness of clomipramine, nefazodone, mirtazapine, fluoxetine and fluvoxamine in GAD. Buspirone, a 5-HTla receptor partial agonist, has been shown to be effective in several placebo-controlled, double-blind trials (Roy-Byme and Cowley, 2002). Buspirone has a later onset of action than both benzodiazepines and SSRIs but with the advantage of being non-addictive and non-sedating. 

In psychomotorically retarded patients, many clinicians prefer to use a less sedating drug (e.g., an SSRI, venlafaxine, bupropion, or desipramine), but definitive evidence is lacking. 

Although the mechanism of action of SSRIs in treating alcohol dependence remains unclear, Gorelick and Paredes ( 432) postulate that it is not due to motor inhibition or general sedation. Rather, they believe it may be related to decreased appetite and food intake or a conditioned taste aversion mediated by increased brain serotonin activity. Other competing theories have been summarized by Thomas ( 433) ... 

The SSRIs, venlafaxine, or nefazodone may be reasonable alternatives to earlier generation antidepressants because of their less problematic side effect profiles (486). The propensity to increase activity, the lack of sedation, gastrointestinal symptoms, and alterations in blood pressure are potential complications, however. Given AIDS-induced altered metabolism, for many of these agents, TDM may be helpful in establishing an effective, nontoxic dose. 

Serotonin syndrome SSRIs, second generation antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St. John s wort, ginseng Hypertension, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma onset within hours Sedation (benzodiazepines), paralysis, intubation and ventilation consider 5-HT2 block with cyproheptadine or chlorpromazine... 

Duloxetine Moderately selective blockade of NET and SERT Acute increase in serotonergic and adrenergic synaptic activity otherwise like SSRIs Major depression, chronic pain disorders fibromyalgia, perimenopausal symptoms Toxicity Anticholinergic, sedation, hypertension (venlafaxine) Interactions Some CYP2D6 inhibition (duloxetine, desvenlafaxine)... 

It is important to point out that basic sleep researchers make mistakes that are every bit as egregious and every bit as persistent as those of our clinical colleagues. From 1969 to 1975, it was widely held that serotonin promoted sleep. If that were true, then the SSRIs would be sedatives, not sleep saboteurs In fact, there is paradoxical sedation in a very high percentage of users, but this effect is not easily attributable to the enhancement of serotonergic efficacy. So strong was the serotonin hypothesis that it worked its way into textbooks, where it lived for fifteen years after it had been clearly shown that serotonin was actually a sleep inhibitor and, reciprocally, a wake-state enhancer. 

In terms of the brain-mind paradigm and its 3-D map, the AIM model, SSRIs produce the equivalent of a stimulant effect as well as paradoxical sedation. The upward shift of the M dimension, caused by the elevation in aminergic drive, makes descent into deep sleep impossible, just as amphetamines make falling asleep at all more difficult. Because subjects spend much more time in light sleep at or near waking levels, they naturally experience more dreaming and they are more aware of it because they awaken more often. 

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