Other tolerability aspects

Clinical laboratory parameters

Analysis of data from placebo-controlled clinical trials (Baldwin et al., 2007) revealed no clinically relevant changes in mean values over time. Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion, has rarely been reported with the use of SSRIs and generally resolves on discontinuation of therapy (Escitalopram SPC, 2007).

Cardiovascular parameters

Escitalopram has no clinically relevant effect on cardiac function,
blood pressure or pulse rate. In pivotal placebo-controlled, 8-week studies, there was a mean decrease in systolic and diastolic blood pressure of 2 ± 12 and 1 ± 9 mmHg, respectively. Pulse rate showed a slight mean decrease of 2 ± 10 bpm (Baldwin et al., 2007).

Body weight

Weight change as a function of body mass index (BMI) showed no significant difference after 24 weeks of treatment with escitalopram or placebo (Baldwin et al., 2007); the mean gains
were 0.58 ± 2.63 kg and 0.15 ± 2.33 kg, respectively.

Seizures

There was no suggestion in the clinical trials database that escitalopram might induce seizures (Baldwin et al., 2007). Like other antidepressants, escitalopram should be discontinued in any
patient who develops seizures (Escitalopram SPC, 2007). As a general recommendation, SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be carefully monitored.

Manic reactions

Reports of mania/hypomania while on escitalopram are extremely rare in the clinical trials database (incidence of hypomania 0.14% and of mania 0%; Baldwin et al., 2007) and in post-marketing surveillance. The incidence for paroxetine in escitalopram studies was 0.78%. SSRIs should be used with caution in patients with a history of mania/hypomania, and discontinued in any patient entering a manic phase (Escitalopram SPC, 2007).

Haemorrhage

There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura with SSRIs (Nelva et al., 2000). Caution is advised in patients taking SSRIs, particularly if they also use drugs known to affect platelet function or they have a history
of bleeding disorders (Escitalopram SPC, 2007).

Enhancement of 5-HT associated effects

Drugs with a monoamine oxidase inhibitor (MAOI) mode of action may interact at the pharmacodynamic level with SSRI antidepressants, including escitalopram. The  recommendations for combination differ, depending on the class of MAOI in question.

• Non-selective, irreversible MAOIs – escitalopram is contraindicated for use with non-selective, irreversible MAOIs, e.g. phenelzine. To ensure adequate ‘washout’, escitalopram
may be started 14 days after discontinuing treatment with an irreversible MAOI and at least 7 days should elapse between discontinuing escitalopram and starting an irreversible MAOI.

• Selective (MAO-A inhibitor), reversible MAOIs – due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-A inhibitor, e.g. moclobemide, is not recommended. If the combination proves necessary, the new treatment should be started at the minimum recommended dose, and additional clinical monitoring is strongly recommended. To ensure
adequate ‘washout’, escitalopram may be started at least 1 day after discontinuing treatment with moclobemide and at least 7 days should elapse between discontinuing escitalopram and
starting moclobemide.

• Selective (MAO-B inhibitor), irreversible MAOIs – due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-B inhibitor, e.g. selegiline, should be undertaken
with caution. If the combination proves necessary, dose reductions should be considered and additional clinical monitoring is recommended.

The combination of SSRIs and MAOIs is a topic under continual investigation and changes in practices and recommendations may occur. Please always consult the local Summary of Product Characteristics for the latest guidance.
Caution should be exercised when co-administering escitalopram with other serotonergic medicinal products, e.g. tramadol, sumatriptan and other triptans (Escitalopram SPC, 2007).

References:

Escitalopram SPC, 2007

Baldwin et al. Ann Pharmacother 2007; 41: 1583-1592

Nelva et al. Rev Med Interne 2000; 21: 152-160