Escitalopram dosing

The antidepressants can be dosed once a day (see Table 69-7). The initial dose of venlafaxine extended-release is 75 mg once a day 37.5 mg can be used in some patients. The dose can be increased every 4 days up to a maximum of 225 mg once daily, although a dose-response relationship has not been established. Paroxetine is administered in a single daily dose (with or without food) of 20 mg. Doses greater than 20 mg/day have not been found to be more effective, but it can be increased by 10 mg/day every week. Escitalopram dosing begins with 10 mg daily. ... 

A meta-analysis of double-blind, randomised, placebo-controlled trials of 2407 patients administered escitalopram at doses between 5 and 20 mg per day in acute (8-12 weeks) and long-term (24 weeks) studies [33 ] found that the mean difference in the QTc interval compared to placebo was 3.5 ms for all escitalopram doses. One of the patients receiving escitalopram developed a QTc interval >500ms and a change from baseline of >60 ms. 

SSRls. SSRI antidepressants have also received considerable scrutiny in the treatment of OCD. Fluoxetine, fluvoxamine, paroxetine, and sertraline are all approved by the FDA for the treatment of OCD. Current studies suggest that each of these medications is more effective for OCD when administered at the higher end of the therapeutic dose range, that is, fluoxetine 60-80 mg/day, fluvoxamine 200-300 mg/ day, paroxetine 40-60 mg/day, and sertraline 150-200 mg/day. No controlled studies are yet available regarding the use of citalopram or escitalopram for OCD. Refer to Chapter 3 for more information regarding SSRl antidepressants. 

In subjects with hepatic impairment, clearance of racemic citalopram was decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg/day. 

Elderly Clearance of fluvoxamine is decreased by about 50% in elderly patients. A lower starting dose of paroxetine is recommended. Sertraline plasma clearance may be lower. In 2 pharmacokinetic studies, citalopram AUC was increased by 23% and 30%, respectively, in elderly subjects as compared with younger subjects, and its half-life was increased by 30% and 50%, respectively. In 2 pharmacokinetic studies, escitalopram half-life was increased by approximately 50% in elderly subjects as compared with young subjects and C ax was unchanged. 

These drugs increase synaptic serotonin by selectively blocking the serotonin reuptake transporter. In preclinical and human studies acute doses tend to be anxiogenic (Bell and Nutt 1998) but chronic administration has anxiolytic effects, possibly due to downregulation of presynaptic autoreceptors (Blier et al. 1990). There are five SSRIs widely available citalopram, fluoxetine, fluvoxam-ine, paroxetine and sertraline. Escitalopram, the S-enantiomer of citalopram. 

Escitalopram was efficacious in patients with major depressive disorder in short-term, placebo-controlled trials, three of which included citalopram as an active control, and in a 36-week study in the prevention of relapse in depression (7). It has also been used to treat generalized anxiety disorder, panic disorder, and social anxiety disorder. Results also suggest that, at comparable doses, escitalopram demonstrates clinically relevant and statistically significant superiority to placebo treatment earlier than citalopram. The most common adverse events associated with escitalopram include nausea, insomnia, disorders of ejaculation, diarrhea, dry mouth, and somnolence. Only nausea occurred in more than 10% of patients taking escitalopram. 

ESCITALOPRAM, FLUOXETINE, FLUVOXAMINE, PAROXETINE, SERTRALINE BUPROPION T plasma concentrations of these SSRIs, with risk of toxic effects Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 Initiate therapy of these drugs at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. paroxetine)... 

Citalopram and escitalopram CYP2C19 PMs may respond better to average doses [47]. CYP2C19 UMs may need higher doses [47,64]. 

The diversity of the SSRIs is evident not only in their chemical structures, but also in their pharmacokinetic profiles. Fluoxetine has an elimination half-fife of 2 to 3 days (4 to 5 days with multiple dosing). The single-dose hah-hfe of norfluoxetine, the active metabolite, is 7 to 9 days. Paroxetine and sertrahne have half-lives of approximately 24 hours. Unlike paroxetine, sertraline has an active metabolite, but the metabohte contributes minimally to the pharmacologic effects. Escitalopram has a half-life of approximately 30 hours. Peak plasma concentrations of citalopram are observed within 2 to 4 hours after dosing, and the elimination half-life is about 30 hours. The SSRIs, with the exception of fluvoxamine, escitalopram, and citalopram, are extensively bound to plasma proteins (94% to 99%). The SSRIs are extensively distributed to the tissues, and aU, with the possible exception of citalopram, may have a nonlinear pattern of drug accumulation with long-term administration. ... 

Venlafaxine extended-release, a serotonin-norepinephrine reuptake inhibitor (SNRI), alleviates anxiety in patients with and without co-morbid depression. The reduction in psychic symptoms of anxiety and tension is not accompanied by significant reductions in somatic symptoms. Venlafaxine (dosed once daily) was effective at doses of 150 and 225 mg for 2 months in patients with GAD, and efficacy was maintained for an additional 6 months of therapy." Paroxetine was significantly more effective than placebo at achieving response in 62% and 68% of patients at 20 and 40 mg daily, respectively, after 2 months. Remission occurred in 30% and 36% of patients taking 20 and 40 mg of paroxetine, respectively." Escitalopram was more efficacious than placebo in three 8-week trials in patients with GAD. In a four paraUel-group comparison, diazepam and trazodone were found to be equivalent in anxiolytic activity (remission rates of 66% and 69%, respectively) compared with placebo (47% remission rate), but rmipramine s rate of remission (73%) exceeded that of the other three treatments. ... 

Patients treated with paroxetine or sertraline showed improvement in anxiety and avoidance symptoms and a decrease in disability. Daily doses up to 60 mg of paroxetine and 200 mg of sertraline were well tolerated, and emergent adverse effects were similar to those of depression trials (e.g., nausea, sexual dysfunction, sweating, and somnolence). The onset of effect was delayed 4 to 8 weeks, and maximum benefit was often not observed until 12 weeks or longer. Sertraline is also effective in disabled patients suffering from the marked to severe form of generalized SAD. Limited data suggest that citalopram, escitalopram, and fluvoxamine are also effective in treating SAD. Fluoxetine was not effective in SAD. ... 

The starting dose for fluvoxamine is 50 mg/day, which is then increased as tolerated and needed up to 300 mg/day divided into twice-daily doses. If citalopram is used, the initial dose is 20 mg/day, and it may be increased to 40 mg/day after 2 weeks. The starting dose for escitalopram is 10 mg/day, and it can be increased to a maximum of 20 mg/day. The dosage should be tapered slowly (i.e., decreasing sertraline by 50 mg/month or paroxetine by 10 mg/month) to decrease... 

The adverse events profile for escitalopram is similar to that observed with Ri-citalopram in both major depression and anxiety disorders. Discontinuation rates due to adverse events were similar in patients receiving escitalopram or placebo in several trials. Nausea and ejaculatory problems were reported in both fully published trials in patients with major depression. In addition, diarrhea, insomnia, dry mouth, headache, and upper respiratory tract infections were experienced by patients receiving escitalopram, although the incidence of these events was not significantly higher than in patients receiving placebo. The recommended dose of escitalopram for the treatment of major depression is 10 mg/day, which, depending on the individual patient response, may be titrated up to 20 mg/day. 

At 20 mg/day of escitalopram (twice the recommended daily starting dose), there is some elevation in levels of coadministered desipramine and metoprolol, which appear comparable to the effect of RS-citalopram.i i 2°... 

The pharmacokinetics for escitalopram does not exhibit stereoisomer selectivity and, therefore, is similar to that for citalopram (Table 21.7). Likewise, it exhibits linear pharmacokinetics so that plasma levels increase proportionately and predictably with increased doses, and its half-life of 27 to 32 hours is consistent with once-daily dosing. It also has been found that R-citalopram is cleared more slowly than the S-enantiomer. Therefore, when the drug is used as a racemic mixture (citalopram), the inactive isomer predominates at steady state. This is an added incentive for use of the enantiomerically pure escitalopram. Escitalopram has negligible effects on CYP isoforms, suggesting a low potential for drug-drug interactions. Escitalopram is... 

Escitalopram. Escitalopram is an inhibitor of the eytoehrome P450 isoenzyme CYP2D6, and may therefore inhibit haloperidol metabolism The manufacturers say that consideration should be given to reducing the dose of haloperidol. ... 

The manufacturers suggest that potent inhibitors of CYP2D6, such as fluoxetine and paroxetine would be expected to increase aripiprazole levels, and they recommend that the dose of aripiprazole should be halved if these drugs are given. The UK manufacturer suggests that weaker inhibitors of this isoenzyme (they name escitalopram) would only be expected to cause modest increases in aripiprazole levels, and therefore no dosage adjustment would expected to be required. ... 

Omeprazole 30 mg daily caused a 50% increase in the plasma levels of escitalopram. This is only a moderate increase, but the manufacturer suggests that caution is warranted and a dose adjustment of the escitalopram may be needed. ... 

A report describes a 74-year-old woman with increased lithium levels of 2.3 mmol/L and symptoms of lithium toxicity, which were associated with several drugs including irbesartan, lisinopril, escitalopram, levomepro-mazine, furosemide and spironolactone. It was suggested that these drugs could have delayed lithium excretion or worsened neurotoxic effects. An increase in the lisinopril dose and the addition of irbesartan several weeks before admission may have contributed to the lithium toxicity. ... 

The authors of the citalopram study say that while cimetidine certainly causes an increase in the serum levels of citalopram, the extent is only moderate and because the drug is well tolerated and there are very considerable pharmacokinetic variations between individual subjects, they consider that there is no need to reduce the citalopram dosage. This advice is most likely applicahle to escitalopram, the S-isomer of citalopram. However, the manufacturer of escitalopram suggests caution, and advises that a reduction in the dose of escitalopram may he necessary (based on monitoring of adverse effects) during concurrent treatment. ... 

Visual hallucinations occurred in a 90-year-old woman taking hydrocodone when her antidepressant was changed from citalopram 10 mg daily to escitalopram 10 mg daily. The hallucinations stopped after her hydrocodone was discontinued because of improvement in pain control. The patient had previously taken paroxetine and the same dose of hydrocodone, without experiencing hallucinations or other serotonin-related symptoms. ... 

Escitalopram 20 mg daily for 21 days increased the maximum serum levels and AUC of a single 50-mg dose of desipramine by 40% and 100%, respectively. The UK manufacturers predict that clomipramine and nortriptyline will be similarly affected. ... 

In a study on the effects of maca for sexual dysfunction induced by selective serotonin reuptake inhibitors (SSRI), patients who were stable on an SSRI (patients were taking escitalopram, citalopram, sertraline, venlafexine, fluoxetine, paroxetine, duloxetine, or fluvoxamine) were orally administered 1.5 or 3 g of maca daily for 12 weeks. No adverse effects of maca, including effects on SSRI efficacy, were reported, and patients in the high dose group had a modest improvement in depression (Dording et al. 2008). 

---