Page 560 - Basic _ Clinical Pharmacology ( PDFDrive )

546 SECTION V Drugs That Act in the Central Nervous System

DOSING dosage recommended or to the highest dosage tolerated if the
patient is not responsive to lower doses. Some patients may ben-
The optimal dose of an antidepressant depends on the indication efit from doses lower than the usual minimum recommended
and on the patient. For SSRIs, SNRIs, and a number of newer therapeutic dose. TCAs and MAOIs typically require titration to
agents, the starting dose for the treatment of depression is usu- a therapeutic dosage over several weeks. Dosing of the TCAs may
ally a therapeutic dose (Table 30–3). Patients who show little or be guided by monitoring TCA serum levels.
no benefit after at least 4 weeks of treatment may benefit from Some anxiety disorders may require higher doses of antide-
a higher dose even though it has been difficult to show a clear pressants than are used in the treatment of major depression. For
advantage for higher doses with SSRIs, SNRIs, and other newer example, patients treated for OCD often require maximum or
antidepressants. The dose is generally titrated to the maximum somewhat higher than maximum recommended MDD doses to
achieve optimal benefits. Likewise, the minimum dose of parox-
etine for the effective treatment of panic disorder is higher than the
TABLE 30–3 Antidepressant dose ranges.
minimum dose required for the effective treatment of depression.
Drug Usual Therapeutic Dosage (mg/d) In the treatment of pain disorders, modest doses of TCAs are
often sufficient. For example, 25–50 mg/d of imipramine might
SSRIs
be beneficial in the treatment of pain associated with a neuropa-
Citalopram 20–60 thy, but this would be a subtherapeutic dose in the treatment of
Escitalopram 10–30 MDD. In contrast, SNRIs are usually prescribed in pain disorders
Fluoxetine 20–60 at the same doses used in the treatment of depression.
Fluvoxamine 100–300
Paroxetine 20–60 ADVERSE EFFECTS
Sertraline 50–200
SNRIs Although some potential adverse effects are common to all anti-
Venlafaxine 75–375 depressants, most of their adverse effects are specific to a subclass
Desvenlafaxine 50–200 of agents and to their pharmacodynamic effects. An FDA warning
Duloxetine 40–120 applied to all antidepressants is the risk of increased suicidality in
patients younger than 25. The warning suggests that use of antide-
Milnacipran 100–200 pressants is associated with suicidal ideation and gestures, but not
Tricyclics completed suicides, in up to 4% of patients under 25 who were
Amitriptyline 150–300 prescribed antidepressant in clinical trials. This rate is about twice
Clomipramine 100–250 the rate seen with placebo treatment. For those over 25, there is
Desipramine 150–300 either no increased risk or a reduced risk of suicidal thoughts and
Doxepin 150–300 gestures on antidepressants, particularly after age 65. Although a
small minority of patients may experience a treatment-emergent
Imipramine 150–300 increase in suicidal ideation with antidepressants, the absence of
Nortriptyline 50–150 treatment of a major depressive episode in all age groups is a par-
Protriptyline 15–60 ticularly important risk factor in completed suicides.
Trimipramine maleate 150–300
5-HT 2 antagonists A. Selective Serotonin Reuptake Inhibitors
Nefazodone 300–500 The adverse effects of the most commonly prescribed
Trazodone 150–300 antidepressants—the SSRIs—can be predicted from their potent
inhibition of SERT. SSRIs enhance serotonergic tone, not just
Tetracyclics and unicyclics in the brain but throughout the body. Increased serotonergic
Amoxapine 150–400 activity in the gut is commonly associated with nausea, gastro-
Bupropion 200–450 intestinal upset, diarrhea, and other gastrointestinal symptoms.
Maprotiline 150–225 Gastrointestinal adverse effects usually emerge early in the course
Mirtazapine 15–45 of treatment and tend to improve after the first week. Increasing
MAOIs serotonergic tone at the level of the spinal cord and above is associ-
ated with diminished sexual function and interest. As a result, at
Isocarboxazid 30–60 least 30–40% of patients treated with SSRIs report loss of libido,
Phenelzine 45–90 delayed orgasm, or diminished arousal. The sexual effects often
Selegiline 20–50 persist as long as the patient remains on the antidepressant but
Tranylcypromine 30–60 may diminish with time.
Other adverse effects related to the serotonergic effects of
MAOIs, monoamine oxidase inhibitors; SNRIs, serotonin-norepinephrine reuptake
inhibitors; SSRIs, selective serotonin reuptake inhibitors. SSRIs and vortioxetine include an increase in headaches and