The patient who got sick at sea
Well-controlled on lithium and fluoxetine, Ms. Q has a hypomanic episode while on a cruise. Is it a breakthrough relapse, SSRI-induced switch, or something else?
Scopolamine, indicated for preventing nausea and vomiting associated with motion sickness, is a centrally acting belladonna alkaloid with primary anticholinergic activity. The agent is thought to block transmission from the vestibular nuclei to higher brain centers and from the reticular formation to the brain’s so-called “vomiting centers.”
The transdermal agent can cause drowsiness, dryness of secretory areas, and impaired motor function. It has no known direct pharmacokinetic interaction with lithium. Use for >5 consecutive days can cause anticholinergic delirium-like states, especially in older patients.
For Ms. Q, scopolamine’s direct anticholinergic action may have destabilized an affective disorder in remission. The putative mechanism of anticholinergic-induced psychosis, delirium, mania, and depression has not been well explained and may differ among these states. The serotonergic and cholinergic systems, however, are assumed to be in a type of balance. Cholinergic deficiencies—as seen in dementia or with medications that have anticholinergic potential—may increase sensitivity to serotonergic tone, thus contributing to Ms. Q’s switch to mania.1
Dr. Schneider’s observations
Ask the patient at each office visit if he or she is concomitantly using an over-the-counter (OTC) medication or a prescription agent from another physician. As with scopolamine, diet pills and oral contraceptives can also destabilize mood or cause depression. Often patients neglect to tell their psychiatrists they started taking an antibiotic, antihypertensive, or other medication since their last visit.
Undetected use of herbal supplements also is a burgeoning clinical problem. Most physicians do not routinely ask patients whether they are using a nonprescription medication, and some clinicians know little about these products’ side effects or interactions with other drugs. Adverse events associated with herbal agents (Table) are difficult to interpret because the purity and amounts of active compounds vary widely.
Table
Mood destabilization, other effects reported after herbal supplement use
| Herbal supplement | Common use(s) | Adverse effects in psychiatric patients |
|---|---|---|
| Dehydroepiandrosterone (DHEA) | Alzheimer’s dementia treatment, body muscle-fat ratio enhancement, stress relief, sexual enhancer | Acute mania when taken with other psychotropics;2 patients with history of affective disorder can exhibit mania when taking DHEA3 |
| Gingko biloba | Cognitive/memory enhancement | Nausea, diarrhea, bleeding in patients taking psychotropics4,5 |
| Massive purpura after concomitant gingko plus citalopram or venlafaxine (clinical experience) | ||
| Ginseng | Stimulant, also purportedly an aphrodisiac | Ginseng-induced mania in two patients with depressive disorders6,7 |
| Horny goat weed | Purported sexual enhancer for men | New-onset hypomania in 66-year-old man after ingesting compound for 2 weeks8 |
| St. John’s wort | Primary or secondary antidepressant | Multiple cases of mania induction, affective destabilization attributed to presumed cytotoxic effects9 |
Appetite suppressants have been reported to cause depression during use or withdrawal,10 but large epidemiologic studies have not determined which diet pills are most associated with depressive symptoms.
Oral contraceptives. Mood changes are an ongoing, noticeable side effect of oral contraceptives11 regardless of whether the patient is taking a psychotropic. Depression is a frequently cited reason for oral contraceptive discontinuation.12
The literature is mixed on how oral contraceptives stabilize or destabilize mood and affect. Hormone-induced mood changes may be caused by:
- estrogen-induced B6 deficiency and subsequent decrease in serotonin and gamma-aminobutyric acid (GABA) because of lower affinity for pyridoxal phosphatate13
- progesterone or estrogen-mediated augmentation of GABA-induced glutamate suppression
- progesterone-mediated increase in mono-amine oxidase activity, leading to lower serotonin concentrations.14
- Physicians’ Desk Reference supplements for over-the-counter medications and nutraceuticals. www.pdr.net/pdrnet/librarian (click on “PDRbookstore”).
- Farley D. How to get the most benefits with the fewest risks. Web MD. https://my.webmd.com/content/article/6/1680_51630.htm.
- Fluoxetine • Prozac
- Haloperdiol • Haldol
- Lithium • Eskalith, others
- Olanzapine • Zyprexa
- Scopolamine • Transderm Scop
Dr. Schneider is a consultant to and speaker for Bristol-Myers Squibb Co., Forest Pharmaceuticals, and Wyeth Pharmaceuticals. He holds research grants from the National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD), the Stanley Medical Research Institute, and the Alzheimer’s Association (Ronald Reagan Research Award).
