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Cases that Test Your Skills

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?

Vol. 4, No. 9 / September 2005

History: Depressed and dropping out

Ms. Q, age 23, presented 6 years ago with a profound anergic depression with suicidal thinking and social withdrawal. This caused her to drop out of high school for approximately 4 months. She also gained 30 lbs across 3 months, further diminishing her low self-image.

At the time, Ms. Q was diagnosed as having unipolar depression. Fluoxetine, 20 mg/d titrated to 40 mg/d, resolved her symptoms before she started college the following year.

Three years later, while continuing on fluoxetine at the same dosage, Ms. Q experienced dysphoric mania, with irritability, grandiosity, and impaired judgment. She was behaving promiscuously during this episode but was not using alcohol or other substances.

After a subsequent manic episode, she was diagnosed with bipolar type I affective disorder. Haloperidol, 10 mg/d for 2 weeks, resolved her mania. She was then maintained on fluoxetine, 50 mg/d, but was not given a mood stabilizer or antipsychotic.

Two years later, I was called in to consult on Ms. Q’s case. She was euthymic and stable at that time but 2 months earlier had experienced a euphoric manic episode characterized by 5 days of racing thoughts, lack of sleep, and manic motoric acceleration. She had stopped seeing her psychiatrist near college and admitted that she needed to work with someone more experienced than her primary care physician in addressing psychiatric symptoms.

When Ms. Q was age 4, her maternal aunt committed suicide via gas poisoning. Also, her paternal grandmother committed suicide before she was born, and her mother had been treated for dysthymia. She has no significant medical history.

Addressing Ms. Q’s bipolar affective disorder poses a clinical challenge. Controlling her mania is a priority but I also need to continue treating her depression, given her significant family history of affective disturbance.

Dr. Schneider’s observations

To address Ms. Q’s mania, I added controlled-release lithium, 900 mg/d, yielding a blood level of 0.9 mEq/L. Ms. Q was not rapid cycling, was taking her fluoxetine as prescribed, and was not abusing alcohol or drugs, so she seemed an appropriate candidate for lithium treatment.

To manage her depression, I cautiously continued fluoxetine, 40 mg/d. The antidepressant had not obviously destabilized her illness, and Ms. Q felt that it allowed her to work and maintain a social life.

Treatment: Cruising and cycling

After 8 months of stability, Ms. Q developed a sudden dysphoric hypomanic episode, with depressed mood, increased energy, racing thoughts, and inability to sleep. She had some insight into her condition and sought consultation with me.

Ms. Q’s parents reported that she had been taking lithium and fluoxetine as prescribed, was taking no other medications, was not using alcohol or drugs, and experienced no unusual stressors, change in diet, or other lifestyle changes. Having her symptoms re-emerge despite faithful medication adherence made Ms. Q extremely anxious and bewildered her and her parents.

Ms. Q later recalled that her parents had taken her on a coastal cruise to Mexico the week before her cycling episode, and that her symptoms emerged while on ship. She began to experience initial and mid-cycle insomnia and was unusually irritable over minor annoyances.

Having seen Ms. Q immediately after the cruise, I added olanzapine, 5 mg nightly for 5 days, to prevent a full-blown manic episode. About 6 days later, she said she was excessively tired, but her insomnia and irritability had ceased. I stopped olanzapine and returned Ms. Q to her previous regimen.

Dr. Schneider’s observations

Ms. Q appeared to have sustained an unexpected relapse into hypomania despite treatment adherence. At this point, I was concerned that:

  • fluoxetine might have destabilized her illness
  • her lithium level decreased without explanation
  • or she had a “breakthrough” relapse while on medication.

Upon returning home, however, Ms. Q’s lithium blood level was 0.8 mEq/L, consistent with prior levels. Also, she had remained stable for 8 months while taking fluoxetine.

Follow-up: A ‘sickening’ discovery

At follow up approximately 1 week later, Ms. Q reported that she had continuously worn scopolamine patches throughout the 8-day cruise to prevent motion sickness. She had forgotten to mention this, however, during our emergency consultation. She had experienced some mydriasis and dry mouth during the cruise but did not remove the patch for fear of seasickness.

On further questioning, Ms. Q said she knew the patch was designed to be used for 2 to 3 days maximum, but added she was responding well to its effects and foresaw no problems with extended use.

Dr. Schneider’s observations

This case illustrates the potentially destabilizing effects of a seemingly innocuous concomitant medication in patients with bipolar disorder.

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.


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)


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

Diet pills. Use of prescription and OTC anorectics is common among weight-conscious Americans.

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

Related resources

Drug Brand Names

  • 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).


1. Cancelli I, Marcon G, Balestrieri M. Factors associated with complex visual hallucinations during antidepressant treatment. Hum Psychopharmacol 2004;19:577-84.

2. Vacheron-Trystram MN, Cheref S, Gauillard J, Plas J. A case report of mania precipitated by use of DHEA. Encephale 2002;28 (6 Pt 1):563-6.

3. Dean CE. Prasterone (DHEA) and mania. Ann Pharmacother 2000;34:1419-22.

4. Gilbert GJ. Gingko biloba. Neurology 1997;48:1137.-

5. Benjamin J, Muir T, Briggs K, Pentland B. A case of cerebral haemorrhage—can Gingko biloba be implicated? Postgrad Med J 2001;77:112-3.

6. Gonzalez-Seijo JC, Ramos YM, Lastra I. Manic episode and ginseng: report of a possible case. J Clin Psychopharmacol 1995;15:447-8.

7. Vazquez I, Aguera-Ortiz LF. Herbal products and serious side effects: a case of ginseng-induced manic episode. Acta Psychiatr Scand 2002;105:76-7.

8. Partin JF, Pushkin YR. Tachyarrhythmia and hypomania with horny goat weed. Psychosomatics 2004;45:536-7.

9. Moses EL, Mallinger AG. St. John’s wort: three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7.

10. Patten SB. “Diet Pills” and major depression in the Canadian population. Can J Psychiatry 2001;46:438-40.

11. Oinonen KA, Mazmanian D. To what extent do oral contraceptives influence mood and affect? J Affect Disord 2002;70:229-40.

12. Goldzieher J. Hormonal contraception: pills, injections, and implants (3rd ed.) London, Ontario: Emis-Canada; 1994.

13. McCarty MF. High-dose pyridoxine as an ‘anti-stress’ strategy. Med Hypotheses 2000;54:803-7.

14. Sherwin B. Hormones, mood, and cognitive functioning in post-menopausal women. Obstet Gynecol 1996;87(suppl 2):20S-26S.

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