Antidepressants dosing

Some studies compare dietary supplements to sub-therapeutic dosages of prescription medicine. For example, St. John s wort is compared to some of the tricyclic antidepressants. However, the given doses of amitriptyline and imipramine were below the recommended antidepressant doses. 

If there is no improvement in the acute stress response 3 to 4 weeks post trauma, SSRIs should be started in a low dose with slow titration upward toward antidepressant doses. Eight to 12 weeks is an adequate duration of treatment to determine response. 

For completeness, buproprion should be mentioned even though it is not widely registered as an antidepressant in Europe, partly because of its propensity to cause seizures in some patients. Buproprion, quite widely used in the USA as an antidepressant, appears to inhibit the reuptake of both dopamine and noradrenaline and therefore tends to have a slightly alerting action. In many European countries it has recently been introduced, at a lower than antidepressant dose, in the treatment of nicotine withdrawal in smoking cessation programmes. 

Treatment with SSRIs is started at or near their therapeutic antidepressant doses. The most significant disadvantage of these medications is a high incidence of treatment-emergent sexual dysfunction (see Sexual Dysfunction subsection later in this section), which often persists for as long as the patient continues taking the medication. 

TCAs derive their name from their chemical structure aU tricyclics have a three-ring nucleus. Currently, most clinicians are moving away from using TCAs as first-line drugs relative to the newer antidepressants, they tend to have more side effects, to require gradual titration to achieve an adequate antidepressant dose, and to be lethal in overdose. Some data suggest that TCAs may be more effective than SSRIs in the treatment of major depression with melancholic features (Danish University Antidepressant Group 1990 Perry 1996) however, many skilled clinicians and researchers continue to prefer the newer antidepressants, even for patients with melancholia, for the aforementioned reasons. Newer medications that affect both norepinephrine and serotonin (e.g., venlafaxine and mirtazapine) also may have superior efficacy in severely iU depressed patients or when remission is defined as the outcome (Thase et al. 2001). 

Because reboxetine and bupropion share with desipramine the ability to block the NE uptake pump, some clinician may want to combine them with an SSRI. Bupropion, however, should be used cautiously with fluvoxamine, fluoxetine, and paroxetine because these three antidepressants inhibit one or more CYP enzymes to a substantial degree at their lowest, usually effective antidepressant dose. Therefore, the dose of bupropion should be kept low and TDM could be used to ensure that unusually high levels of bupropion or its active metabolites do not develop. 

TABLE 7-29. Effects of specific SSRis on specific CYP enzymes at their respective, usually effective, antidepressant dose... 

SSRIs sometimes cause an initial jitteriness similar to that noted with initial imipramine therapy for PD. This may be more common with SSRIs than with other currently available non-TCA antidepressant therapies for PD. Just as low initial imipramine doses avert this reaction, initiating SSRI therapies with one fourth to one half the usual starting antidepressant dose followed by gradual increments with low doses can avert this reaction. This syndrome can also be blocked by add-on, low-dose, as-needed BZD therapy (e.g., alprazolam or lorazepam). 

Janiri L, Gobbi G, Mannelli P, et al. Effects of fluoxetine at antidepressant doses on short-term outcome of detoxified alcoholics. Int Clin Psychopharmacol 1996 11 109-117. 

Maintenance doses will be higher than starting doses, and may need to be higher than usual antidepressant doses, particularly for paroxetine. 

Activation should be at the top of the differential diagnosis list when a patient s condition deteriorates while taking antidepressants. If the physician misidentifies drug-induced activation as caused by the patient s original psychiatric disorder, the doctor is likely to continue, or even increase, the antidepressant dose, ultimately causing mania and psychosis. 

Paroxetine metabolism at low concentrations is dependent on CYP2D6, which is almost saturated at these concentrations, Thus, there are non-linear pharmacokinetics and an increase in the half-life of paroxetine from 10 to 20 hours when the dose is increased from lOmg to 20mg, At higher concentrations, the metabolism is mainly by CYP3A4 isoenzymes, Paroxetine inhibits the activity of CYP2D6 in the lowest usually effective antidepressant dose,... 

When switching from anofher antidepressant or adding to another antidepressant, dosing may need to be lower and titration slower to prevent activating side effects (e.g., 2 mg in the daytime for 2-3 days, fhen 2 mg bid for f-2 weeks)... 

For insomnia, initial 25-50 mg at bedtime increase as tolerated, usually to 50-100 mg/day, but some patients may require up to fuii antidepressant dose range... 

Antidepressant medications have been shown to often be helpful in chronic pain syndromes. These medications are effective only for chronic pain and not for acute pain. They help reduce pain and, when combined with narcotic analgesics, potentiate the effects of the narcotic. The cyclic antidepressants are the best studied and have the most supporting evidence. When there is not an accompanying depression, lower than the usual antidepressant doses may be effective. Venlafaxine, because of its similarities to the cyclic antidepressants, is probably effective also. There are a few studies showing the effectiveness of the SSRIs, but some studies that do not. 

The results of our study focusing on antidepressant dosing at the time of discharge tend to corroborate previous evidence that African American patients need lower doses of TCAs than do Caucasian patients. Results are more equivocal with respect to our study of African American and Caucasian patients taking SSRIs. However, when weight is taken into consideration, it is found that African Americans might need lower doses of SSRIs compared with Caucasians. 

Adverse Effects. Typical antidepressant doses of SSRIs can cause side effects of insomnia, jitteriness, restlessness, and agitation, and lead to drug discontinuation in patients with panic disorder. Transient gastrointestinal disturbances occur more frequently with SSRIs than with TCAs. Thus low initial SSRI doses should be prescribed. Sleep disturbances, headaches, and sexual dysfunction often are problematic. ... 

Dosing and Administration. SSRIs should be initiated at doses similar to those used for the treatment of depression and administered as a single daily dose with or without food (except for fluvoxamine). If the patient suffers from comorbid panic disorder, the SSRI dose should be started at one-fourth or one-half of the normal antidepressant dose. Patients should receive the starting dose for 2 to 4 weeks before it is increased slowly (i.e., paroxetine 10 mg/day and sertraline 50 mg/day) in weekly intervals as necessary to obtain a response. Safety for paroxetine in SAD was demonstrated in doses up to 60 mg/day, but additional therapeutic benefits above 20 mg/day were not shown. The maximum dosage of sertraline used in patients with SAD was 200 mg/day. ... 

For women with premenstrual exacerbation of an underlying depression, severe PMDD, or climacteric depression, a 6- to 12-month course of an antidepressant is recommended. Some women benefit from continuous antidepressant dosing with an intermittent increase in dose prior to the onset of symptoms and a reduction in dose at the onset of menses. Varying the antidepressant dosage and adding supplemental medications based on menstruation-related symptoms have been shown empirically to be helpful. It may be necessary to try several different treatments to find an acceptable therapy. 

Many studies have been done comparing St. John s wort to placebo or to tricyclic antidepressants (Linde et al., 1996). However, problems with inclusion criteria, diagnostic criteria, antidepressant dosing, and study duration do not permit definitive conclusions about the safety and efficacy of St. John s wort for treatment of depression. 

This case, however, was quite unusual in that the phototoxic reaction was provoked by UV-B light, while hypericin 1 is known to absorb UV-A wave-lengths, and the morphology of the skin reaction was rather atypical. No other case of a phototoxic skin reaction on antidepressant doses of Hypericum extracts has been reported in the literature so far. 

In conclusion, even under steady state treatment with twice the dose recommended for depressive disorders, only a minimal increase in daylight sensitivity was found along with a mildly enhanced tanning reaction. This ties in with the results of in vitro and animal studies and the fact that only one case of phototoxicity in a patient taking the antidepressive dose has been documented thus far. And even this case is of questionable relevance because of atypical features. 

Adverse drug reactions should be considered if a patient does not do well after treatment begins if restlessness or agitation oocur, increasing antidepressant doses can be detrimental. 

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