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CASES THAT TEST YOUR SKILLS Mr. J is disoriented and seeing ‘visions.’ His psychiatric history suggests a substance use disorder, but a screen is negative. How would you diagnose him?

The consequences of sipping ‘tea’

Melissa Buboltz, MD ® SahanaDowden Misra, MD Health MediaLinda Ganzini, MD, MPH Resident Assistant professor Professor Department of psychiatry Associate residency training director Departments of psychiatry CopyrightForDepartment personal of psychiatry use only and medicine Oregon Health & Science University, Portland

HISTORY: A 'NEGATIVE' VIEW trist, who has prescribed , 40 mg/d, for r. J, a 50-year-old native of , has had depres- depression and , 1 mg three times daily, M sion and disorder for more for related anxiety symptoms. than 10 years, marked by irritability, poor sleep, The patient is disoriented and inattentive during hopelessness, and suicidality. He also suffered a the mental status examination. His cognitive deficits traumatic brain injury in the military 25 years ago. fluctuate in severity; at times he is aware of his sur- Police bring Mr. J to the ER after they find him roundings, then suddenly loses this awareness. wandering near traffic and speaking incoherently. Vital signs are stable. Physical exam shows Mr. His feet and hands jerk on the way to the hospital, J is approximately 30 lb underweight (97 lb) with a leading police to suspect that Mr. J has suffered a body mass index of 16.9 kg/m2—nearly 2 kg/m2 grand mal seizure. below normal. He says he has been skipping meals In the ER, Mr. J appears confused, has visual because of poor appetite. He also has strikingly hallucinations, and moves his hands and feet invol- lizard-like, scaly skin. untarily. His head and arms move erratically during Urine drug screen shows no signs of recent the ER psychiatrist’s interview, and he says that his or substance abuse. Complete metabolic pelvis is arching forward and preventing him from profile shows elevated , suggesting walking steadily. The day before, he says, he saw alcohol or illicit substance toxicity, toxic- frightening “visions” of a being who looked “like a ity, hepatitis, thyroid disorder, muscle disease, or a photo negative.” rare liver condition. EEG shows mild encephalopa- Mr. J has been seeing an outpatient psychia- thy but no ictal activity.

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Mr. J suffers from: a) substance intoxication/withdrawal How would you b) seizure disorder handle this case? c) depression with psychotic features d) substance-induced delirium Visit www.currentpsychiatry.com to input your answers and compare them with e) substance-induced psychotic disorder those of your colleagues

The authors’ observations Although the test results narrow the differen- Our psychiatric differential diagnosis is broad: tial diagnosis, we still have to consider numerous • visual and auditory hallucinations are con- medical conditions that can cause delirium, such current in numerous disorders, including as trauma, cerebral vascular accident, intracerebral and depression masses, CNS infection, and inflammatory disease. • visual hallucinations alone suggest demen- tia, delirium, or resulting from a medical condition, medication, or sub- Which tools could help clarify Mr. J’s stance(s) of abuse1 diagnosis? • Mr. J’s past head injury increases his risk of a) additional laboratory testing dementia and delirium b) imaging • his abrupt symptom onset and inattention c) collateral information suggest delirium. Police feared that Mr. J suffered a seizure dur- ing transport to the ER, but EEG shows no ictal HISTORY: COLLATERAL CONTRIBUTIONS activity. Also, his abnormal motor movements e refer Mr. J for lumbar puncture to rule out appear choreoathetoid, alternating between brief, W CNS infection and MRI to rule out tumor, rapid, involuntary movements () and slow, abscess, or other structural brain abnormalities that continuous, writhing movements (athetosis). could cause seizure. Results are unremarkable. Choreoathetosis can result from: We then speak with Mr. J’s outpatient psychia- • such as and levodopa trist, who reports that Mr. J has had no residual • toxins cognitive impairment from his head injury. She • systemic diseases such as systemic lupus adds, though, that he often develops cognitive erythematosus, thyrotoxicosis, or stroke problems after consuming large amounts of a tradi- • degenerative brain diseases such as tional South Pacific beverage containing ( Huntington’s disease methysticum). She explains that Mr. J socializes • or focal brain diseases such as tumors.2 with fellow who drink kava at gatherings, Given Mr. J’s substance abuse history, we and that he often drinks kava to excess. She attrib- strongly suspect a substance-related disorder utes his dry, scaly skin to excessive kava use. despite the negative urine drug screen. Alcohol Upon questioning, Mr. J says he consumes withdrawal is unlikely because his vital signs are about a half-pound of kava per day. He says he stable, and the negative drug screen rules out uses the root to make a tea-like beverage that, like withdrawal. alcohol, induces and relaxation. He says

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• Mr. J’s cognitive symptoms are more severe Box than those caused by kava intoxication Kava: A popular alternative • his psychotic symptoms occur only when to prescription he is delirious • his disturbed consciousness, cognitive, Kava, extracted from the of Piper methysticum, acts as a , and perceptual disturbances and the tem- , and .5 It is among the poral relationship between symptom most commonly used alternative treatments onset and massive kava use match DSM- for psychiatric symptoms, with sales estimated IV-TR criteria for substance-induced at $17 million in the in 2004.6 delirium.4 Kava lactones, the pharmacologically Cultural use. Although Mr. J’s kava consumption active components of kava, might act via constitutes abuse, people in some cultures ingest several pathways, including GABA-A herbal substances as part of spiritual or social ritu- 7 binding and dopaminergic antagonism. This als. Fijians, for example, commonly drink kava at GABAergic CNS activity affects similar receptors as do and produces social gatherings or ceremonies. kava’s anxiolytic effects. Being aware of cultural customs and beliefs Kava is available in health food stores as in your practice area can alert you to herbal sub- capsules, tinctures, and fluid extracts and can stance use in various populations, such as kava be obtained without a prescription. The by patients from the South Pacific or echinacea, amount of active ingredient varies greatly goldenseal, and burdock by some Native from preparation to preparation. Americans (see Related resources). Medicinal use. Patients often use kava and other herbal supplements—including fatty acids, gink- he began doing this in his youth back in Fiji, and go biloba, ginseng, St. John’s wort, , and now drinks “many cups” of kava per day. others—with or instead of prescription to Mr. J states that his current episode of strange alleviate psychiatric symptoms. Complementary movements and visual hallucinations began hours and alternative medicine practitioners use kava to after he drank several cups of kava the day before treat anxiety, for example (Box). police brought him to the ER. He considers his Anxiety and depression are among the most new psychiatric symptoms Jesus’ punishment for common reasons persons seek complementary or drinking kava. alternative treatment. In a national survey, 57% of respondents who suffered “anxiety attacks” and 54% of those with “severe depression” The authors’ observations reported using such therapies.8 Nearly 1 in 5 per- Mr. J’s persecutory suggest that he does sons who take prescription drugs also take not fully associate his symptoms with excessive and/or high-dose vitamin supplements.9 kava use, but his abnormal movements, weight Herbal products have been shown to cause loss, skin changes, liver function abnormalities, adverse effects (Table 1).10 Kava, for example, has and mental status changes are known adverse been associated with , dermopathy, effects of kava.3 We diagnose substance-induced movement disorders, GI disturbance, and weight delirium rather than substance intoxication or loss. Standardized extracts such as capsules and substance-induced psychosis because: tinctures appear more likely to cause adverse

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Table 1 Possible adverse effects of herbal supplements used for psychiatric symptoms

Medication Psychiatric uses Adverse effects

Fatty acids Depression, GI upset

5-HTP Depression, anxiety Agitation, ataxia, blurred vision, bradycardia, (5-hydroxytryptophan) dyspnea, , headache, hypotension, , mania, psychosis, tremulousness

Ginkgo Cognitive Bleeding, dizziness, GI upset, headache, (Ginkgo biloba) enhancement palpitations, Stevens-Johnson syndrome

Ginseng Cognitive Estrogenic effects, insomnia, mania (Panax ginseng) enhancement

Kava Anxiety Dermopathy, drowsiness, dry mouth, (Piper methysticum) GI disturbance, hepatotoxicity, weight loss, movement disorders,

SAM-e Depression, Constipation, diarrhea, increased salivation, (S-adenosyl-L-methionine) headache, , urinary frequency, mania in patients with

St. John's wort Depression Anorexia, anorgasmia, anxiety, constipation, () dizziness, dry mouth, fatigue, GI upset, mania, photosensitivity, pruritis, restlessness, urinary frequency

Valerian Insomnia Drowsiness, GI upset, headache, (Valeriana officinalis) hepatotoxicity

Source: Reference 10

effects than traditional extractions, such as a bev- (SSRIs)12 and can reduce blood levels of psychotrop- erage made by infusing kava root.5 ics metabolized by the cytochrome P-450 3A4 isoen- Kava toxicity has been reported among zyme, such as and . heavy users. Although the dosage at which kava Mr. J combined kava with clonazepam. Both becomes dangerous is unknown, the FDA rec- substances affect gamma-aminobutyric (GABA) ommends that users not exceed typical dosages receptors, increasing the risk of by (50 to 280 mg/d) and use kava only under a depressing the CNS. physician’s supervision.11 Also, interactions between herbal products and allopathic medications can cause substantial mor- ASK ABOUT ALTERNATIVE MEDICINE USE bidity (Table 2, page 136). St. John’s wort, for exam- According to a national survey,13 many patients do ple, can lead to serotonin syndrome when combined not tell allopathic physicians they are using com- with selective serotonin inhibitors plementary or alternative medications because:

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Table 2 Potential adverse interactions between psychotropics and complementary/alternative medications

Herb Interacts with … Interaction can cause … 5-HTP carbidopa, MAOIs, SSRIs delirium, serotonin syndrome Ginseng MAOIs mania Kava first- and second-generation sedation , benzodiazepines, MAOIs SAM-E TCAs serotonin syndrome St. John's wort benzodiazepines, beta blockers, serotonin syndrome (w/SSRIs) , carbamazepine, , MAOIs, SSRIs, TCAs, reduced plasma levels of cytochrome P-450 3A4 substrates, diminishing their effectiveness Valerian benzodiazepines sedation MAOIs: Monoamine oxidase inhibitors SSRIs: Selective serotonin reuptake inhibitors TCAs:

• “It wasn’t important for the doctor to Knowing whether your patients are using know.” complementary or alternative medications is crit- • “The doctor never asked.” ical to avoiding drug-drug interactions, prevent- • “It was none of the doctor’s business.” ing adverse side effects, and ensuring effective • “The doctor would not understand.” treatment. Yager et al14 suggest that you: • or “The doctor would disapprove or dis- • routinely question patients about use of courage CAM use.” alternative therapies • discuss safety and efficacy of commonly used alternative treatments • discuss merits of alternative treatments Kava and other herbal preparations can • provide information on the effectiveness cause adverse side effects or and risks of various treatments interact negatively with prescription • learn about alternative therapies by con- medications. Routinely ask patients if sulting the Physicians’ Desk Reference they are taking nonprescription (PDR) for Herbal Medicines or similar ref- supplements, and counsel them on erences intelligent use of alternative treatments. • help patients make decisions about alter- native treatments, such as finding a quali-

Bottom Line fied, licensed alternative provider.

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continued from page 136 TREATMENT: QUICK RESOLUTION Related resources e admit Mr. J to the inpatient psychiatry unit.  National Center for Complementary and Alternative Medicine. W There, we continue his outpatient prescrip- http://nccam.nih.gov. tion medications at the same dosages and block  Physicians Desk Reference (PDR) for herbal medicines, 3rd ed. access to nonprescription substances. His symp- Montvale, NJ: Thomson PDR; 2004.  Ernst E, Pittler MH, Stevinson C, et al. The desktop guide to toms begin to improve during the first day of hospi- complementary and alternative medicine. Edinburgh, UK: Mosby; talization. His choreoathetosis, hallucinations, and 2001. confusion resolve within 48 hours, and he is med- DRUG BRAND NAME ically stable. Alprazolam • Xanax Citalopram • Celexa We discharge Mr. J after 2 days and continue Buspirone • BuSpar Clonazepam • Klonopin Carbamazepine • Equetro, others Clozapine • Clozaril citalopram and clonazepam at the same dosages. Carbidopa • Lodosyn Trazodone • Desyrel

The authors’ observations DISCLOSURES The authors report no financial relationship with any company whose products Kava reaches peak plasma levels 1.8 hours after are mentioned in this article, or with manufacturers of competing products. oral dosing and has a short (9-hour) elimination half-life. As a result, kava intoxication symptoms 3. De Smet PA. Health risks of herbal remedies: an update. Clin tend to resolve rapidly, as in Mr. J’s case. Pharmacol Ther 2004;76:1-17. Although Mr. J is medically stable, liver dam- 4. Diagnostic and statistical manual of mental disorders, 4th ed, text rev. age associated with kava use can be irreversible, Washington, DC: American Psychiatric Association; 2000;143-5. 5. Whitton PA, Lau A, Salisbury J, et al. Kava lactones and the kava- prompting some European countries to ban its kava controversy. 2003;64:673-9. sale. Make sure patients who report kava use are 6. Nutrition Business Journal: Top 100 selling U.S. supplements sales aware of its hepatotoxicity risk. & growth, 1999-2004. Available at: http://tdaf.nutrition4texas.org/ meetings/files/2006TDA_Paul_Thomas_Top100.pdf. Accessed October 13, 2006. FOLLOW-UP: KICKING THE KAVA HABIT 7. Pittler MH, Ernst E. Efficacy of kava extract for treating anxiety: wo weeks after Mr. J’s discharge, his psychi- and meta-analysis. J Clin Psychopharmacol 2000;20:84-9. T atrist notes that his mental status has 8. Kessler RC, Soukup J, Davis RB, et al. The use of complementary returned to baseline and that his skin has improved and alternative therapies to treat anxiety and depression in the dramatically. The patient is following his citalopram United States. Am J Psychiatry 2001;158:289-94. 9. Eisenberg DM, Davis RB, Ettner SL, et al. Trends in alternative and clonazepam regimen, and he seems more medicine use in the United States, 1990-1997: results of a follow- aware of kava’s potential adverse effects. up national survey. JAMA 1998;280:1569-75. Mr. J reports that he has not consumed kava 10. Werneke U, Turner T, Priebe S. Complementary medicines in psychiatry: review of effectiveness and safety. Br J Psychiatry 2006; since his hospitalization. He has been eating four 188:109-21. meals per day and has gained 9 lb. He is pleased 11. Medline Plus. Kava (Piper methysticum G. Forst). Available at: with his improved appetite and is motivated to con- http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient- kava.html. Accessed October 13, 2006. tinue abstaining from kava. 12. Izzo AA. Ernst E. Interactions between herbal medicines and prescribed drugs: a systematic review. Drugs 2001;61:2163-75. 13. Eisenberg DM, Kessler RC, Van Rompany MI, et al. Perceptions References about complementary therapies relative to conventional therapies 1. Moore DA, Jefferson J. Handbook of medical psychiatry, 2nd ed. among adults who use both: results from a national survey. Ann New York: Elsevier/Mosby; 2004:8. Intern Med 2001;135:344-51. 2. Nagagopal V. Movement disorders. In: Noble J, Greene HL, 14. Yager J, Siegfreid SL, DiMatteo TL. Use of alternative remedies by Levinson W, eds. Textbook of primary care medicine, 3rd ed. New psychiatric patients: illustrative vignettes and a discussion of the York: Elsevier/Mosby; 2001:1530-1. issues. Am J Psychiatry 1999;156:1432-8.

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