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1. Selective serotonin reuptake inhibitors (SSRIs)

fluoxetine
20-60 mg, once daily in am
$1.08-3.25/day

or fluvoxamine
100-300 mg/day; maximum hs dose 150 mg, remainder in am
$1.41-4.23/day

or paroxetine
20-50 mg, once daily
$1.59-3.28/day

or sertraline
50-200 mg, once daily with evening meals
$1.60-3.50/day

OR

2. Heterocyclic antidepressants (secondary amines)

protriptyline
15-40 mg, divided tid
$0.52-1.39/day

or maprotiline
25 mg, tid (maximum 150 mg/day divided bid to tid)
$0.62-1.07/day

or desipramine
75-300 mg, hs
$0.63-2.54/day

OR

3. Reversible monoamine oxidase inhibitors (MAOIs)

moclobemide
100 mg, tid(maximum of 200 mg, tid)
$1.20-2.40/day

OR

4. Serotonin-2 antagonist

nefazodone
150-300 mg, bid
$1.96-3.92/day

Second-line therapies:

1. Serotonin-norepinephrine reuptake inhibitors for those refractory to drugs of choice

venlafaxine
75 mg, bid to tid(maximum 125 mg, tid)
$3.12-7.02/day

2. Heterocyclic antidepressants (tertiary amines) for patients unable to afford drugs of choice and who can tolerate the side effects (orthostatic hypotension or anticholinergic symptoms)

amitriptyline
75-150 mg, hs(maximum 300 mg/day)
$0.02-0.09/day

or imipramine
75-150 mg, hs(maximum 300 mg/day)
$0.03-0.11/day

or trimipramine
75-150 mg, hs(maximum 250 mg/day)
$0.52-0.88/day

3. Classical MAOIs, to be used in consultation with a psychiatrist

tranylcypromine
10 mg, bid morning and afternoon; maintenance dose may be lower
$0.67/day

or phenelzine
45-90 mg/day, in 3 divided doses; maintenance dose may be lower
$0.89-1.80/day

Additional instructions and notes

-Clinical outcomes, quality-of-life outcomes and overall treatment costs provide no clear guidance on initial selection of fluoxetine or tricyclic antidepressants. At present, there is insufficient evidence to support the use of SSRIs as a cost-effective first-line treatment compared with tricyclic antidepressants. Choice of drug should be made on the basis of side-effect and risk profile on an individual basis.

-There is no difference in efficacy between SSRIs and heterocyclic antidepressants.

-Antidepressants must be tested for a sufficient time before being changed: heterocyclic antidepressants, 3 weeks; SSRIs, 4-6 weeks; MAOIs, 4 weeks.

-Before switching to a different class of antidepressants, patients can be referred to a mood disorder clinic for either augmentation or combination therapy. Augmentation therapy involves adding lithium or triiodothyronine to the antidepressant; combinations of SSRIs and heterocyclic antidepressants may also be successful.

-In drugs with long half-lives, make dosage adjustments slowly.

-Fewer patients on SSRIs drop out due to side effects compared with tricyclic antidepressants. This difference may be due to the use of tertiary amines as reference compounds. Compared with secondary amines, the SSRIs do not show a statistically significant difference in discontinuation rates.

-The risk of suicide is similar in patients on SSRIs and heterocyclic antidepressants. If there is a difference, the cost per life year gained through the routine use of SSRIs is likely to be high.

-Tricyclic antidepressants appear to be no more effective than placebo in the treatment of depression in children and adolescents.

-Based on current controlled trials, in depressed elderly patients there are no significant differences with respect to efficacy and tolerability rates among tricyclic antidepressants, SSRIs and MAOIs.

-According to a meta-analysis, St. John’s wort seems to be as effective as standard antidepressants for short-term treatment (8 weeks) of depression. Long-term measures of efficacy and side effects are lacking and it is unclear which preparation to use.

-Sympathomimetics (dextroamphetamine, methylphenidate, magnesium pemoline) are not recommended for use in primary care.

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