Paradoxical Reactions to Benzodiazepines: Literature Review and Treatment Options

Carissa E. Mancuso, PharmD; Maria G. Tanzi, PharmD; Michael Gabay, PharmD


Pharmacotherapy. 2004;24(9) 

Alprazolam and Temazepam


Manic types of symptoms, including increased energy, racing thoughts, and insomnia, were reported in three patients treated with alprazolam.[5] The first patient, a 32-year-old woman, had an 8-year history of depressive bipolar disease, which was well controlled by drugs. She experienced manic types of symptoms after receiving alprazolam 0.5 mg 3 times/day as needed for anxiety. In the second case, a 34-year-old man with a 5-year history of anxiety sought medical attention for increased panic attacks. Alprazolam was started and titrated to 1 mg 3 times/day. The man had no relief of anxiety; however, he experienced irritable behavior and insomnia. The third patient was a 32-year-old woman with a history of panic attacks due to heights and elevators. After taking alprazolam 1 mg/day, she reported feeling agitated, irritable, and restless. In all three cases, alprazolam was discontinued and the paradoxical reactions ceased within 48-72 hours. The authors concluded that alprazolam may induce symptoms resembling mania in patients with no history of affective disorder. They also noted that no specific characteristics define patients at risk for these adverse reactions.


Uncharacteristic agitation and angry behavior were described in four patients treated for insomnia with temazepam.[10] The first patient, a 30-year-old woman with a medical history of manic depressive symptoms, became enraged after taking temazepam 30 mg at bedtime for 4 days. The second patient was a 30-year-old man who became agitated with temperamental outbursts after receiving temazepam 30 mg at bedtime for 6 days. The man had broken dishes in the middle of the night but had no recollection of that event. In the third case, a 37-year-old man with a medical history of schizophrenia awoke from sleep with much anger after taking temazepam 30 mg. In the final case, a 39-year-old woman experienced sleeplessness and agitation when taking temazepam. These problems occurred while she received temazepam 15 mg and 30 mg at bedtime. In the first and third patients described above, temazepam was stopped and reinitiated with the same response. In all four patients, once temazepam was discontinued, the anger and agitation ceased.