Caffeine and Panic Attacks

Caffeine is more than a mild stimulant that adds punch to coffee and soft drinks; its ability to provoke severe anxiety in some people may provide important clues to the biology of panic attacks, according to research teams at Yale University and the National Institute of Mental Health (NIMH). 

          A dose of caffeine equal to about eight cups of coffee produces far greater increases in anxiety, nervousness, fear, nausea and restlessness among patients diagnosed for panic disorder than among healthy volunteers, report the Yale investigators in the March ARCHIVES OF GENERAL PSYCHIATRY. Dennis S. Charney, George R. Heninger and Peter I. Jatlow studied 17 healthy subjects and 21 patients with agoraphobia (the fear of being alone or, paradoxically, in public places) and panic attacks or panic disorder. A panic attack is characterized by severe emotional and physical distress that usually lasts for a few minutes, it is estimated that 2 to 5 percent of the population have panic disorder -- repeated panic attacks with no apparent external cause.

Fifteen of the 21 patients reported symptoms similar to those of panic attacks after receiving an eight-cup dose of caffeine. Five of the 17 control subjects reported panic attack symptoms.

Thomas W. Uhde of NIMH says that among the panic disorder patients he and his colleagues have studied, caffeine doses equal to about four cups of coffee bring on panic attacks in 40 percent of the subjects; healthy controls report no rise in anxiety at the same dose. But in a study published last year in PSYCHOPATHOLOGY that contrasts with the Yale report, the NIMH researchers observed no significant differences between the anxiety attacks of five panic patients and eight healthy controls given a caffeine dose comparable to almost eight cups of coffee.

Nevertheless, both groups say that their studies, when combined with related research, suggest that caffeine blocks the action of adenosine, a chemical that reduces the spontaneous firing of neurons in several brain regions. Both caffeine and yohimbine, a drug with similar anxiety producing effects, may increase the flow of calcium into neurons, a process controlled by adenosine, say the Yale scientists. More calcium may activate more brain cells, they explain, leading to greater anxiety.

This is a promising research lead, notes Eric Reiman of Washington University in St. Louis, but sodium lactate offers a more established model for mimicking naturally occurring anxiety or panic attacks. Using a positron emission tomography (PET) scanner, Reiman and colleagues identified a blood flow imbalance between the left and right sides of one part of the brain in 7 out of 10 panic disorder patients (NATURE, Aug. 23, 1984). This imbalance may prove to be a genetic marker for panic disorder, he says. The same seven patients were the only subjects who experienced panic attacks after receiving an infusion of sodium lactate, Reiman points out. The mechanism by which sodium lactate causes panic is unclear, he adds, but his research group is examining reactions to the substance more closely.

Not all patients with panic disorder report severe anxiety responses to caffeine, sodium lactate or yohimbine. The 70 percent who do may represent a subgroup with specific biological problems, but it is too early to tell, says Reiman.

The definition of panic attacks is also in a formative stage. Says Heninger of Yale: "Panic researchers are having a difficult time defining the difference between anxiety symptoms and a full-blown panic attack. This is creating difficulty in interpreting the data from various laboratories."