LaryngoSCOPE Common Otolaryngologic Medications: Psychiatric Side Effects Steven Levy, M.D., Mona M. Abaza, M.D., Mary Hawkshaw, R.N., B.S.N., CORLN, Robert Thayer Sataloff, M.D, D.M.A. Singing teachers may be the first ones to observe symptoms and signs of medical problems in their students; and they often serve as a student's primary resource and advi- sor on a variety of issues, including medical issues. Most singers consult an otolaryngologist at some time during their careers, often on the recommendation of their teachers. Many singers also experience peri- ods of stress, agitation, and emotion- al lability. A singing teacher is often the first person called upon to help a singer understand and work through these problems and com- pensate for them. It is important for singing teachers to recognize that not all such problems are the result of a "high strung" personality, preperformance anxiety, or even in- trinsic psychological problems. Some of the problems are iatrogenic (caused by medical treatment). In some cases, psychological distur- bances may be caused by extremely common medications, prescribed of- ten for singers by otolaryngologists and ordinarily tolerated well, with- out negative side effects. Conse- quently, it is helpful for singing teachers to be familiar with some of the psychiatric disturbances that can be caused by medications their stu- dents may be taking. The resulting psychological disturbances are some- times indistinguishable from prima- ry psychiatric disorders; and they can cause disturbing dysfunction in normal life activities, as well as in- terfere substantially with the ability to perform. Many medications may also have adverse effects on the voice by interfering with vocal fold lubrica- tion and function, lung function and support for singing, or other bodily functions essential to singing; but these effects are not discussed in this article and may be reviewed in other literature. Certain medications routinely prescribed by otolaryngologists may have negative psychiatric side effects that can include mood disturbances, such as agitation, anxiety, depres- sion, and mania; perceptual distur- bances, such as hallucinations and delusions; cognitive disturbances, such as delirium and confusion; and behavioral disturbances, such as in- somnia. The combination of some of the medications prescribed by oto- laryngologists with previously pre- scribed psychotropic drugs (general- ly prescribed by a psychiatrist) may enhance or interfere with the thera- peutic effects of one or the other medications. In addition to negative psychiatric side effects, adverse reac- tions such as cardiac arrhythmias and hypertension have also been seen. It should be noted that psychi- atric symptoms manifesting at any time during the course of treatment are not always solely side effects of medication, but may be a manifesta- tion of a coexisting or preexisting psychiatric disorder aggravated by the combination of medications a patient may be taking. The manifestations of drug-in- duced psychiatric disorders may be related to direct drug toxicity or in- terference with the brain's metabo- lism of the drug(s). The most com- mon psychiatric symptomatology includes delirium (an acute reaction with fluctuating awareness of self and environment), confusion, dis- orientation, tremor, ataxia, and ma- nia with behaviors such as increased activity, rapid speech, insomnia, and mood elevation. Psychiatric symp- tonis presenting during the course of treatment may also be related to the medical or psychiatric condition be- ing treated. Anxiety disorders and panic attacks are known to occur in association with thyroid, parathy- roid, adrenocortical disorders; Langhen's cell endocrinopath ies; collagen vascular disorders (such as systemic lupus erythematosus, rheumatoid arthritis, temporal ar- teritis, and periarteritis nodosa); and neurotological disorders such as multiple sclerosis and Ménière's dis- ease. 2 Delusions (the perception that one's environment and circum- stances seem unfamiliar) may also 54-fg 2001 35 ci, No- c, tf , 3S--40 2001 N4z,4 AZ4
Transcript
LaryngoSCOPE
Common Otolaryngologic Medications: Psychiatric Side Effects
Steven Levy, M.D., Mona M. Abaza, M.D., Mary Hawkshaw, R.N., B.S.N., CORLN, Robert Thayer Sataloff, M.D, D.M.A.
Singing teachers may be the first ones to observe symptoms and signs of medical problems in their students; and they often serve as a student's primary resource and advi-sor on a variety of issues, including medical issues. Most singers consult an otolaryngologist at some time during their careers, often on the recommendation of their teachers. Many singers also experience peri-ods of stress, agitation, and emotion-al lability. A singing teacher is often the first person called upon to help a singer understand and work through these problems and com-pensate for them. It is important for singing teachers to recognize that not all such problems are the result of a "high strung" personality, preperformance anxiety, or even in-trinsic psychological problems. Some of the problems are iatrogenic (caused by medical treatment). In some cases, psychological distur-bances may be caused by extremely common medications, prescribed of-ten for singers by otolaryngologists and ordinarily tolerated well, with-out negative side effects. Conse-quently, it is helpful for singing teachers to be familiar with some of the psychiatric disturbances that can be caused by medications their stu-dents may be taking. The resulting psychological disturbances are some-times indistinguishable from prima-
ry psychiatric disorders; and they can cause disturbing dysfunction in normal life activities, as well as in-terfere substantially with the ability to perform.
Many medications may also have adverse effects on the voice by interfering with vocal fold lubrica-tion and function, lung function and support for singing, or other bodily functions essential to singing; but these effects are not discussed in this article and may be reviewed in other literature.
Certain medications routinely prescribed by otolaryngologists may have negative psychiatric side effects that can include mood disturbances, such as agitation, anxiety, depres-sion, and mania; perceptual distur-bances, such as hallucinations and delusions; cognitive disturbances, such as delirium and confusion; and behavioral disturbances, such as in-somnia. The combination of some of the medications prescribed by oto-laryngologists with previously pre-scribed psychotropic drugs (general-ly prescribed by a psychiatrist) may enhance or interfere with the thera-peutic effects of one or the other medications. In addition to negative psychiatric side effects, adverse reac-tions such as cardiac arrhythmias and hypertension have also been seen. It should be noted that psychi-atric symptoms manifesting at any
time during the course of treatment are not always solely side effects of medication, but may be a manifesta-tion of a coexisting or preexisting psychiatric disorder aggravated by the combination of medications a patient may be taking.
The manifestations of drug-in-duced psychiatric disorders may be related to direct drug toxicity or in-terference with the brain's metabo-lism of the drug(s). The most com-mon psychiatric symptomatology includes delirium (an acute reaction with fluctuating awareness of self and environment), confusion, dis-orientation, tremor, ataxia, and ma-nia with behaviors such as increased activity, rapid speech, insomnia, and mood elevation. Psychiatric symp-tonis presenting during the course of treatment may also be related to the medical or psychiatric condition be-ing treated. Anxiety disorders and panic attacks are known to occur in association with thyroid, parathy-roid, adrenocortical disorders; Langhen's cell endocrinopath ies; collagen vascular disorders (such as systemic lupus erythematosus, rheumatoid arthritis, temporal ar-teritis, and periarteritis nodosa); and neurotological disorders such as multiple sclerosis and Ménière's dis-ease. 2 Delusions (the perception that one's environment and circum-stances seem unfamiliar) may also
Steven Levy, Mona M. Abaza, Mary Hawkshaw, Robert Thayer Sataloff
acetic in association with certain cii-docrinopathies. 2 Derealization (the feeling that familiar events seem un-real, strange, and dream-like and that colors, objects, and shapes ap-pear distorted), as well as delusions have been reported in systemic lu-pus erythematosus.2
RISK FACTORS FOR DRUG-
INDUCED PSYCHIATRIC DISORDERS
As always, a detailed history will help a clinician assess individual patient risk and should include the following questions. What prescrip-tion medications and over-the-counter medications is the patient currently taking? Are there coexist-ing medical conditions that can cause psychiatric symptoms? Is there a previous history or family history of psychiatric disorder? Has the disorder presented at an unusual age or in an atypical form? Is there a history of substance abuse? Is there a history of previous psychiatric drug reaction?
The patient's age is also an im-portant factor when deciding what medication(s) to prescribe. Elderly patients are at greater risk for drug-induced psychiatric disorders, as they tend to be on more medications and are, therefore, more likely to en-counter drug-interactions. Older pa-tients also tend to have other med-ical conditions that prolong drug metabolism, which increases sys-temic drug levels.
Preexisting organic brain dis-ease can also be a risk factor in the development of negative psychiatric side effects, as can drug abuse. Pa-tients with a history of drug depen-
dence or abuse commonly manifest delirium. The presence or history of a mood disorder, either depression or mania, is also a risk factor for ex-periencing psychiatric side effects to medications. Adrenocorticosteroids can aggravate or unmask the depres-sion or mania in these patients. Even a family history of mania is a risk factor for the development of mania as a side effect.1
Assessment of all risk factors is important, as multiple factors in a particular patient may be additive. The overall low incidence of psychi-atric side effects for a particular medication may increase in the pres-ence of other factors. Understanding risks in an individual patient is es-sential in the selection of medica-tions prescribed by an otolaryngolo-gist. Clinicians should routinely ask patients to bring in, or list, all med-ications they have used in the last two months. Clinicians should also inquire as to whether or not a pa-tient has experienced any side ef-fects or abnormal reactions from any medications previously taken.
NEGATIVE PSYCHIATRIC SIDE EFFECTS OF SPECIFIC
MEDICATIONS
Steroids Adrenocorticosteroids are well
known to cause psychiatric side ef-fects. Mood disorders such as de-pression and mania, behavioral changes such as insomnia, psy-chosis, and delirium are not uncom-mon. The symptoms tend to be pro-portional in incidence and to the dosage and duration of the steroid use. latrogenic Cushing's syndrome, caused by long-term steroid use, may
also manifest with psychiatric SYIIIp-
toms including mood changes, de-pression, euphoria, or mania 1 (Table l).4
A personal or family history of affective mental illness may predis-pose a patient to negative psychiatric side effects of steroids. 3 Severe de-pression may require antidepressant treatment. Antipsychotic medica-tions, or mood stabilizers, such as di-vaiproex sodium (Depakote) or lithi-um carbonate, may be necessary to treat steroid-induced mania. Insom-nia, as an isolated side effect or as part of a manic episode, may also re-quire medical intervention.
Antihistamines and Decongestants
Antihistamines and deconges-tants, alone and in combination with each other, can cause psychi-atric side effects due to the various components in common prepara-tions. 34 Table 2 shows some of the drug-induced psychiatric disorders associated with specific medica-tions. These medications may be particularly troublesome, because many antihistamines and deconges-tants can be purchased over-the-counter (OTC) and are consumed without physician supervision. Moreover, some people do not even
realize that their OTC medications include antihistamines and decon-gestant components. Also, some people do not regard over-the-counter medications as "medi-cines," and thus do not report them as part of their medical history un-less specific inquiries are made. Medications containing phenyl-propanolamine, phenylephrine, and pseudoephedrine are contraindicated with monamine oxidase (MAO) in-hibitors, as they can inhibit antide-pressants such as pheneizine sulfate (Nardil) and tranylcypromine sulfate (Parnate). They can produce danger-ously high levels of norepinephrine, as the MAO inhibitors impair the metabolism of the sympathomimet-ic medications. 5 High levels of norepi-nephrine can cause hypertensive cri-sis, agitation, or acute psychosis. Table 3 lists some specific medica-tions to avoid in combination with monoamine oxidase inhibitors.6
Sympathomimetic medications, by themselves, may also cause nega-tive psychiatric side effects. Young children, as well as elderly patients with organic brain syndrome, are most vulnerable. Discontinuing the suspected medication, or sedation with lorazepam (Ativan), oxazepam (Serax), or treatment with a high po-tency antipsychotic medication such as haloperidol (Haldol) may be nec-essary. Low potency antipsychotic drugs such as thioridazine (Mellaril) or chlorpromazine (Thorazine) should be avoided with phenyl-propanolamine, because the combi-nation can cause hypotension. The antihistamine and anticholinergic components of a combination anti-histamine/decongestant can produce an atropine-like psychosis, typically including confusion, disorientation,
Agitation, Anxiety, Nervousness
Delirium, Confusion
Depression
Hallucinations
Mania, Hypomania, Euphoria
Sleepiness
Phenyipropanolamine
Phenylephrine
Pseudoephedrine
Over-the-counter Medications
* Specifically: Nardil and Parniite
agitation, hallucinations, and memo-ry deficits. Agitation can be treated with short-acting, nonanticholiner-gic sedatives such as lorazepam (Ati-van) or oxazepam (Serax). Severe agitation or psychotic symptoms can be treated with low doses of haloperidol (Haldol). Clearing of the mental status after administra-tion of physostigmine 7 confirms
Trinalin (azatidine) Claritin (loratidine)
Entex LA (phenyipropanolamine hydrochloride/guiafenesin)
Clantin
Claritin
Trinalin, Entex PSE (pseudoephedrine HCL/guafenesin)
Trinalin
Trinalin, Allegra (fexofenadine)
Entex LA
Extendryl Neosynephrine Phenergan VC
I)uratuss-I) Entex PSE Sudafed Trinalin (2laritin-L)
Sinus medications, hay-fever medications, nasal decongestants, cough and cold preparations
the diagnosis of atropine-like psy-chosis. The symptoms should re-solve completely after the suspect-ed medication is discontinued.
The metabolism of many med-ications by the liver is mediated by certain cytochrome P450 hepatic en-zymes) The antidepressants fluvoza-mine (Luvox) and nefazodone (Ser-zone) interfere with certain P450
*Agents containing pseudoephedrine, phenjjl pro panolamine, or phengi-ephrine can cause agitation, anxiety, nervousness, hallucinations, mania, hgpomania, euphoria, and paranoia.
+ Agents containing phengi pro panolamine can cause delirium, confision. and depression. Agents containing phenglephrine can cause panic attacks.
TABLE 3. Some Sympathonimetic Agents Contraindicated with Mono-amine Oxidase Inhibitors*
H4/J1 2001 37
Steven Levy, Mona M. Abaza, Mary Hawkshaw, Robert Thayer Sataloff
coenzymes. 8 When these antidepres-sants are prescribed with other med-ications metabolized by the same isoenzymes, competition between the medications for the isoenzyme impairs the ability to be metabolized as efficiently as usual. This can cause blood levels of these medications to become dangerously high, causing significant side effects or even a fatal reaction. 8 The antidepressants dis-cussed above cannot be used in com-bination with terfenadine (Seldane) or astemizole (Hismanol) for these reasons. (It should be noted that Sel-dane is off the market, but Hismanol is still available by prescription.) Lo-ratidine (Claritin), fexofenadine (Al-legra), and cetinizin (Zyrtec) can be used with these antidepressants, as they are metabolized by a different c.vtochrome P450 isoenzyme.
Ref lux Medications Laryngopharyngeal reflux is
an extremely common entity that has been recognized and treated widely by otolaryngologists in re-cent years. '° The condition is diag-nosed especially frequently among patients with voice complaints. An-tisecretory medications (decrease stomach acid production) are com-monly used in the treatment of re-flux laryngitis. There are two cate-gories: the competitive antagonists or histamine H-2 receptors, includ-ing famotidine (Pepcid), nizatidine (Axid), ranitidine (Zantac), and cimetidine (Tagamet); and the pro-ton-pump inhibitors including omeprazole (Prilosec), lansoprazole (Prevacid), and others.
All H-2 antagonists have been associated with some negative psy-chiatric side effects. 1 ' Table 4 pro-vides a list of commonly prescribed
Aggression, Hostility, Violence
Confusion, Delirium, Mania, Hypomania, Euphoria
Somnolence
Depression
Hallucinations
Paranoia
reflux medications and their associ-ated psychiatric side effects, which include cognitive and mood changes, and delirium mediated by the central nervous system (CNS), which is the most common. The overall incidence of these side effects with these agents in outpatients is less than 0%2 The incidence increases significantly in hospitalized patients, the elderly, the seriously ill, and those with he-patic or renal failure. Higher doses of the medications commonly used in the treatment of laryngopharyngeal reflux, as well as other drugs, may in-crease the risk of side effects with an-tireflux medications.
Negative psychiatric side effects of H-2 antagonists may vary in their time of onset of treatment and re-solve within three days of discontin-uing the medication, but this may vary. For example, Ranitidine (Zan-tac) has caused depression with an onset 4-8 weeks after the initiation of treatment. Cimetidine (Tagamet)
Taga met (cimetidine), Zantac (ranitidine), Prilosec (omeprazole), Prevacid (lansoprazole)
Tagamet (cimetidine)
has shown adverse effects within 2-3 weeks after the initiation of treatment and has even caused delir-ium within 24-48 hours. 11 The dis-continuation of Zantac and Tagamet has been associated with a with-drawal syndrome including anxiety, insomnia, and irritability. 1:1 Tagamet may increase the blood level and ac-tion of tricyclic antidepressants such as amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor), and doxepin HCI (Sinequan), elevat-ing the levels of these anti-depres-sants to toxic levels and causing tachycardia and other negative side effects. Inhibition of the cytochrome P450 enzymes by H-2 antagonists (Tagamet and Zantac) can also lead to potentially dangerous side effects with certain other psychiatric med-ications. Tagamet is the most potent inhibitor of this enzyme system, but other H-2 antagonists are weaker in-hibitors. Zantac is between one-fifth to one-tenth as potent an inhibitor
TABLE 4. Drug-Induced Psychiatric Side Effects ofAnti-Secretory Agents
as Tagamet. Pepcid and Axid do not inhibit this enzyme system at all. 11
Tagamet will increase the half-life of the antianxiety medications chlorazephate (Tranxene), chlor-diazepoxide (Librium), and di-azepam (Valium) to a greater degree than Zantac) 1 A lower dose of these long-acting benzodiazepenes should be considered when they are given to a patient taking Tagamet. The al-ternative use of short-acting benzo-diazepenes such as oxazepam (Ser-ax) and lorazepam (Ativan) can be considered, as well. The metabolism of these antianxiety medications is not affected by Tagamet or Zantac." Alternatively, different antireflux medications can be selected.
Tagamet can also increase the blood levels of antidepressants such as the tricyclics and the sero-tonin reuptake inhibitors, antipsy-chotic medications, and anticon-vulsants such as Tegretol.'4-'7 Lower doses of these medications should be given when used in com-bination with Tagamet, if possible. The blood levels of these medica-tions can be monitored periodically and the doses of the medications adjusted accordingly. Using a dif-ferent H-2 antagonist, such as Pep-cid or Axid, is also an option.
The combination of the proki-netic medication cisapride (Propul-sid) with the antidepressants nefaze-done (Serzone) and fluvoxamine (Luvox) is of particular concern.8 Serzone and Luvox decrease the me-tabolism of Propulsid and elevate blood levels causing a fatal ventricu-lar arrhythmia.8 This combination is listed as a contraindication on the drug product information.
Another prokinetic medication, metoclopramide (Reglan), is much
safer to use in combination with those medications, but has been as-sociated with depression and other neurological side effects.411
CONCLUSION
Many medications prescribed commonly by otolaryngologists can cause negative psychiatric side effects. Serious drug interactions from the combination of some of these medications and other psychi-atric medications can also occur and are potentially fatal. An awareness of the potential for negative psychi-atric side effects of adrenocorticos-teroids, antihistamine/deconges-tants, and antisecretory medications helps in the avoidance, detection, and treatment of these drug-induced disorders. An awareness of the po-tential for severe side effects caused by the combination of medications commonly prescribed by otolaryn-gologists with certain psychiatric medications will help prevent these adverse reactions and help in the se-lection of the appropriate medica-tions for individual patients. Know-ing individual patient risk factors such as age, preexisting organic brain disease, a history of drug abuse or dependence, and preexisting or coexisting psychiatric disorder is im-portant in preventing and detecting drug-induced psychiatric disorders. Singing teachers should be particu-larly aware of these negative side ef-fects, as even mild manifestations may interfere with ability to concen-trate and with vocal quality and vo-cal performance; and conditions of-ten go misdiagnosed for a prolonged time before the iatrogenic nature of a problem is recognized by the singer or otolaryngologist.
REFERENCES
1. Sataloff RT, Hawkshaw MJ, Ca-puto Rosen D. Medications: ef-fects and side-effects in profes-sional voice users. In: Sataloff RT, Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, Calif: Singular Pub-lishing Group; 1997:457-469.
2. Othmer E, Sieglinde SC. The
Clinical Interview Using DSM-IV Vol.1. Washington, DC., American Psychiatric Press Inc; 1994:252-259.
3. Bernstein JG. Handbook of Drug Therapy in Psychian-y. St. Louis, Mo: Mosby; 1995:370-371.
4. Bazire 5, Benefield JR,William H. Psjjchologic Drug Directory 1997-8. West Orange, NJ: Quay Books; 1997:217-236.
5. Bernstein jG. Handbook of Drug Therapy in Psychiatry. St. Louis, Mo: Mosby; 1995:353.
6. Bernstein 1G. Handbook of Drug Therapy in Psychiatry. St. Louis, Mo: Mosby; 1995:546.
7. Bernstein .JG. Handbook of Drug Therapy in Psychiatry. St. Louis, Mo: Mosby; 1995:384.
8. Stahl SM. Psychopharmacology of Antidepressants. London: Dunitz Ltd; 1997:101-108.
9. Sataloff RT, Castell DO, Sataloff M, Sataloff D, Spiegel J. Reflux and other gastroenterologic con-ditions that may affect the voice. In: Sataloff RT. Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, Calif: Singular Publish-ing Group Inc; 1997:319-329.
10. Sataloff RT, Castel] DO, Katz P0, Sataloff DM. Reflxv Laryn-gitis and Related Disorders. San Diego, Calif: Singular Publish-ing Group Inc; 1999.
H4./& 2001 39
Steven Levy, Mona M. Abaza, Mary Hawkshaw, Robert Thayer Sataloff
11 Bernstein JG. Handbook o(T) rug Therapy in Ps,ychiatrij. St. Louis, Mo: Mosby; 1995:380-381.
12. Canter TG, Korec, JS. Central nervous system reaction to his-tamine-2 receptor blockers. Ann Intern Med. 1991;14:1027-1034.
13. Nicoletti G, Rampell L. The H2-antagonist therapy withdraw syndrome. Medicina (Firenze).
July-September, 1990;10(3):299-306.
14. Bernstein JG. Handbook of Drug Therapy in Psychiatry, St. Louis, Mo: Mosby;1995:346.
15. Bazire S, Benefield JR,Williarn H. Psychologic Drug Directory 1997-8. West Orange, NJ: Quay Books; 1997: 179.
16. Bazire S, Benefield JR.,William H. Psychologic Drug Directory
1997-8. West Orange, NJ: Quay Books; 1997:166.
17. Bernstein JG. Handbook of Drug Therapy in Psychiatry. St. Louis, Mo: Mosby;1995:359.
Steven Levy, MD, is Research Associate Psychiatrist with the American Institute fbr Voice and Ear Research in Philadephia, Pennsylvania. Mona M. Abaza, MD, is As-
sistunt l-'rofcs.cr of Orolarijwjoloqjj—I-Iead and Neck Surqt7y at the University of Col-orado Health Science Center and at the WilburJanes Gould Voice Research Center in Denver, Colorado. Mary Hawkshaw, RN., B.S.N., CORLN, isan Otolarjngolog-ic Nurse Clinician and researcher with the American Institute for Voice and Ear Re-search in Philadelphia, Pennsylvania. Robert Thayer Sataloff, M.D., DMA., is Professor of Otolaryngology—Head and Neck Surgery at Thomas Jefferson Univer-sity, Chairman of the Department of Oto-laryngology —Head and Neck Surgery at Graduate Hospital in Philadelphia, Penn-sylvania. He also is Chairman of the Board of Directors of the Voice Foundation.
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