Seroxat

J Clin Psychiatry 2002 Sep;63(9):772-7
A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone.
Kampman M, Keijsers GP, Hoogduin CA, Hendriks GJ
Department of Clinical Psychology and Personality, University of Nijmegen, The Netherlands

BACKGROUND: Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone. METHOD: 161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo. RESULTS: Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0. CONCLUSION: Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized.

GENERIC NAME: paroxetine
BRAND NAME: Paxil, Paxil CR

DRUG CLASS AND MECHANISM: Paroxetine is an anti-depressant drug that affects the chemicals that nerves in the brain use to communicate with one another. These chemical messengers, called neurotransmitters, are released by one nerve and taken up by other nerves. Neurotransmitters that are released but not taken up by other nerves are taken up by the nerves that release them ("reuptake"). Many experts believe that it is an imbalance among the amounts of the different neurotransmitters that are released that causes depression. Paroxetine works by inhibiting the reuptake of serotonin by the nerves that release it, an action which allows more serotonin to be available to be taken up by other nerves. Paroxetine is in a class of drugs called selective serotonin reuptake inhibitors (SSRIs), a class that also contains fluoxetine (Prozac) and sertraline (Zoloft).

PREPARATIONS: Tablets (oval): 10 mg (yellow), 20 mg (pink), 30 mg (blue), and 40 mg (green). Paxil CR, a controlled release form of paroxetine, is available in tablets of 12.5, 25, and 37.5 mg.

STORAGE: Tablets should be kept at room temperature, 15- 30°C (59-86°F).

PRESCRIBED FOR: Paroxetine is indicated for the management of depression, obsessive-compulsive disorders, panic disorders, and premenstrual dysphoric disorder.

DOSING: Paroxetine is given as a single daily dose, usually in the morning. As with all anti-depressants, the full effect may not occur until after a few weeks of therapy. Doses for obsessive- compulsive disorders and panic disorders are often higher than those for depression. Doses often are adjusted to find the optimal dose. Elderly patients, debilitated persons, and patients with certain kidney or liver diseases may need lower doses because they metabolize and eliminate paroxetine more slowly and, therefore, are prone to develop high blood levels.

DRUG INTERACTIONS: All SSRIs, including paroxetine, should not be taken with any of the MAO (mono-amine oxidase) inhibitor-class of anti-depressants, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane). Such combinations may lead to confusion, high blood pressure, tremor, and increased activity. This same type of interaction may also occur with selegiline (Eldepryl), fenfluramine (Pondimin), and dexfenfluramine (Redux). The anti-ulcer medication, cimetidine (Tagamet) can increase the amount of paroxetine in the blood, possibly leading to side effects. Paroxetine may increase the risk of bleeding in patients taking warfarin (Coumadin) although the mechanism for the interaction is not known. Tryptophan can cause headaches, nausea, sweating, and dizziness when taken with any SSRI. Phenytoin (Dilantin) and phenobarbital may decrease the amount of paroxetine in the body and possibly reducing its effectiveness.

Paxil CR is approved for continuous or intermittent therapy for premenstrual dysphoric disorder. For intermittent therapy, women take Pacil CR once daily during only the two-week period prior to the onset of their menstrual cycle rather than throughout the month.

PREGNANCY: There are no adequate studies of paroxetine in pregnant women.

NURSING MOTHERS: It is not known if paroxetine is secreted in breast milk.

SIDE EFFECTS: The most commonly noted side effects associated with paroxetine are anxiety, sweating, nausea, decreased appetite, somnolence (sleepiness), dizziness, insomnia, and male sexual disturbances. Dry mouth occurs in about 18% of patients taking paroxetine.

The withdrawal of treatment with many anti-depressants has been associated with troublesome symptoms. Symptoms have been particularly frequent with anti-depressants, like paroxetine, classified as SSRI's. Specifically, the incidence of symptoms upon withdrawal is between 17% and 30% with paroxetine and fluvoxamine (Luvox), but less than 5% with other SSRI's.

The most common symptoms of withdrawal have been dizziness, tiredness, tingling of the extremities, nausea, vivid dreams, irritability, and poor mood. Other symptoms have included visual disturbances and headaches.

Withdrawal reactions have been reported upon withdrawing SSRI's after an average of 12 to 36 weeks of treatment, but after as few as 5 weeks. Although most authorities have recommended that treatment be discontinued by tapering the SSRI (by gradually reducing the dose), symptoms have occurred despite tapering. Symptoms generally appear within a few days of discontinuing medication and persist for an average of 12 days (up to 21 days). They are relieved within 24 hours by re-administering the medication that was discontinued.

It has been suggested that SSRIs may cause depression to worsen and even lead to suicide in a small number of patients. These potential side effects are difficult to evaluate in depressed patients because depression can progress with or without treatment, and suicide is itself a consequence of depression. Moreover, the evidence supporting these potential side effects is weak. Therefore, no conclusions can yet be drawn about the relationship between SSRIs and worsening depression and suicide. Until better information is available, patients receiving SSRIs should be monitored for worsening depression and suicidal tendencies.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.