CASE From soft-spoken to manic
Mr. K, age 36, an Asian male with no psychiatric history, arrives at the outpatient psychiatry clinic accompanied by his wife, after being referred from the emergency room the night before. He reports racing thoughts, euphoric mood, increased speech, hypergraphia, elevated self-esteem, decreased need for sleep, distractibility, and increased goal-directed activity. Notably, Mr. K states that he likes how he is feeling.
Mr. K’s wife says that his condition is a clear change from his baseline demeanor: soft-spoken and mild-mannered.
Mr. K reports that his symptoms started approximately 10 days earlier, after he returned from a cruise with his wife. During the cruise, he used a scopolamine patch to prevent motion sickness. Mr. K and his wife say that they believe that the scopolamine patch caused his symptoms.
Can scopolamine cause mania?
a) No
b) Yes; this is well-documented in the literature
c) It is theoretically possible because of scopolamine’s antidepressant and central anticholinergic effects
TREATMENT Lithium, close follow up
Mr. K has no history of psychiatric illness or substance use and no recent use of psychoactive substances—other than scopolamine—that could trigger a manic episode. His family history is significant for a younger brother who had a single manic episode at age 12 and a suicide attempt as a young adult.
Mr. K works full-time on rotating shifts—including some overnight shifts—as a manufacturing supervisor at a biotechnology company. He has been unable to work since returning from the cruise because of his psychiatric symptoms.
Mr. K is started on sustained-release (SR) lithium, 900 mg/d. In addition, the psychiatrist advises Mr. K to continue taking clonazepam, 0.5 to 1 mg as needed, which the emergency medicine physician prescribed, for insomnia. Mr. K is referred to a psychiatric intensive outpatient program (IOP), 3 days a week for 2 weeks, and is advised to stay home from work until symptoms stabilize.
Mr. K follows up closely with the psychiatrist in the clinic, every 1 to 2 weeks for the first month, as well as by several telephone and e-mail contacts. Lithium SR is titrated to 1,200 mg/d, to a therapeutic serum level of 1.1 mEq/L. Clonazepam is switched to quetiapine, 25 to 50 mg as needed, to address ongoing insomnia and to reduce the risk of dependency on clonazepam.
Mr. K’s mania gradually abates. He finishes the IOP and returns to work 3 weeks after his initial presentation. At an office visit, Mr. K’s wife gives the psychiatrist 2 scientific articles documenting the antidepressant effect of scopolamine.1,2 Mr. K and his wife both continue to believe that Mr. K’s manic episode was triggered by the scopolamine patch he used while on the cruise. They think this is important because Mr. K believes he would not have developed mania otherwise, and he does not want to take a mood stabilizer for the rest of his life.
The author’s observations
There are several proposed mechanisms for scopolamine’s antidepressant effect (Table 1).3-9 Scopolamine blocks central muscarinic cholinergic receptors, which reduces production of glutamate receptors and leads to reduced glutamate transmission and neurotoxicity.3,4 Scopolamine—similar to ketamine—could enhance synaptogenesis and synaptic signaling.5,6 Also, by blocking muscarinic autoreceptors, scopolamine results in an acute upregulation of acetylcholine release, which, in turn, influences the nicotinic, dopamine, serotonin, and neuropeptide Y systems. This action could contribute to anti-inflammatory effects, all of which can benefit mood.7-9 These antidepressant mechanisms also could explain why, theoretically, scopolamine could precipitate mania in a person predisposed to mental illness.
Proposed by Janowsky et al10 in 1972, the cholinergic−adrenergic balance hypothesis of affective disorders suggests that depression represents an excess of central cholinergic tone over adrenergic tone, and that mania represents the opposite imbalance. Several lines of evidence in the literature support this theory. For example, depressed patients have been found to have hypersensitive central cholinergic receptors.11,12 Also, central cholinesterase inhibition has been shown to affect pituitary hormone and epinephrine levels via central muscarinic receptors.13 In addition, scopolamine has been shown to attenuate these effects via the central anti-muscarinic mechanism.14
Rapid antidepressant therapy. Scopolamine is being studied as a rapid antidepressant treatment, although it usually is administered via IV infusion, rather than patch form, in trials.15-17 IV ketamine is another therapy being investigated for rapid treatment of depression, which might have downstream mechanisms of action related to scopolamine.5,18 Electroconvulsive therapy is a well-known for its quick antidepressant effect, which could involve synaptogenesis or effects on the neuroendocrine system.19 Sleep deprivation also can produce a rapid antidepressant effect20 (Table 21,2,5,6,15,16,18-20).
OUTCOME Prone to motion sickness
Approximately 3.5 months after his initial presentation, Mr. K continues to do well with treatment. He is euthymic and functioning well at work. He and his wife are preparing for the birth of their first child.