Adverse effects associated with the short-term treatment of panic disorder with imipramine, alprazolam or placebo

Abstract

Side effects play a significant role in the selection of drugs to be used in panic disorder/agoraphobia whose polyphobic symptomatology often includes a suspiciousness about taking drugs and a fear of undesired side effects which may lead to the refusal of treatment. The safety, side effects and patients' acceptance of alprazolam and imipramine versus placebo were evaluated in 1168 subjects with panic disorder/agoraphobia who had been enrolled in the second phase of the Upjohn World Wide Panic Study. Side effects that worsened over baseline to a greater extent with alprazolam than with imipramine and placebo were sedation, fatigue/weakness, memory problems, ataxia and slurred speech. In the imipramine group blurred vision, tachycardia/palpitations, insomnia, sleep disturbance, excitement/nervousness, malaise, dizziness/faintness, headache, nausea/vomiting and decrease in appetite were worse than in the other groups. In the placebo group the anxious symptoms were most prominent. The highest level of compliance was shown in the alprazolam-treated group and the lowest in the placebo-treated group. Strong predictors of side effects were not observed. If a side effect profile is known, it will be easier for a clinician to choose the right drug and the appropriate management by taking into account compliance, safety and efficacy in each patient under treatment. Further information about side effects in long-term maintenance treatment would be of great clinical pertinence in ensuring safety and enhancing patients' quality of life.

Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature

“…Generally, adverse effects diminished during treatment, but were still present at the end of the study. Analysis of the number of adverse events reported in the second CNCPS showed marked differences between the treatments (39). Patients using alprazolam reported an increment in typical adverse effects of benzodiazepines, such as sedation, fatigue, weakness, memory problems, ataxia and slurred speech, whereas patients using imipramine reported an increment in anticholinergic adverse effects such as blurred vision, tachycardia, palpitations, insomnia, nervousness, malaise, dizziness, headache, nausea, vomiting, and decreased appetite.…”

Selective serotonin reuptake inhibitors and benzodiazepines in panic disorder: A meta-analysis of common side effects in acute treatment

“…Fatigue, defined as a sensation in which the individual feels weak and with lack of motivation, was evaluated in SSRI and BZ trials. SSRIs and BZs were compared to placebo across 1381 and 2155 PD patients, respectively (Asnis et al, 2001; Ballenger et al, 1998; Cassano et al, 1994; Cross-National Collaborative Panic Study, 1992; Lecrubier et al, 1997; Londborg et al, 1998; Lydiard et al, 1992; Noyes et al, 1988; Pollack et al, 1998; Sheikh et al, 2000). Fatigue was reported in 880 SSRI and 501 placebo-treated patients.…”

“…Daytime somnolence was compared in 903 SSRI and 524 placebo-treated patients. It was also evaluated in 799 patients comparing 399 BZ to 400 acute PD patients treated with placebo (Asnis et al, 2001; Ballenger et al, 1998; Cassano et al, 1994; Lecrubier et al, 1997; Londborg et al, 1998; Pollack et al, 1998; Sandmann et al, 1995; Sheikh et al, 2000; Valença et al, 2000). Both drugs increase somnolence during the day (BZs: OR=4.59; p =0.03; CI 1.12–18.72; I 2 =32%; SSRIs: OR=2.03; p <0.01; CI 1.36–3.02; I 2 =4%).…”

“…Acute BZ treatment of 1129 PD patients was compared to administration of placebo to 1108 patients to evaluate constipation. BZs presented as a risk factor for constipation (OR=2.52; p <0.01; CI 1.84–3.46; I 2 =0%; Andersch et al, 1991; Cassano et al, 1994; Cross-National Collaborative Panic Study, 1992; Lydiard et al, 1992; Noyes et al, 1988). Although three studies evaluated this adverse event, comparing 613 SSRI with 288 placebo-treated patients (Ballenger et al, 1998; Lecrubier et al, 1997; Wade et al, 1997), we could not find a risk or a protector effect for this class of drugs (CI 0.56–1.98).…”

ALPRAZOLAM: profilo farmacoeconomico nei disturbi d’ansia e da attacchi di panico

“…Gli effetti collaterali e le reazioni avverse ad alprazolam sono generalmente ben tollerate e vengono per lo più accettate dai pazienti che raramente sospendono il trattamento. (54,55) Le reazioni avverse più frequenti consistono in un'accentuazione degli effetti farmacologici dell'alprazolam a livello del SNC e sono rappresentate da sonnolenza, depressione, torpore, stanchezza, vertigini. Talvolta il paziente manifesta fenomeni paradossi come cefalea, insonnia, irrequietezza.…”