Vol. 107 No. 4 April 2009

MEDICAL MANAGEMENT AND PHARMACOLOGY UPDATEEditors: F. John Firriolo and Nelson I. Rhodus

Postoperative psychosis in an adolescent subsequent to oralsurgical outpatient procedureVishal Bansal, BDS, MDS,a Sanjeev Kumar, BDS, MDS, FDS, RCPS,b

Apoorva Mowar, BDS, MDS,c Sachin Sharma, MBBS, MD,d and Surbhi Gupta, MBBS, MD,e

Meerut, IndiaSUBHARTI DENTAL COLLEGE

Psychosis is a generic psychiatric term for a mental state often described as involving a “loss of contact withreality.” People experiencing psychosis may report hallucinations or delusional beliefs, and they may exhibitpersonality changes and disorganized thinking. This may be accompanied by unusual or bizarre behavior, as well asdifficulty with social interaction and impairment in carrying out the activities of daily living. Psychiatric complicationsduring the course of surgical treatment are well recognized and may range from acute psychotic episodes to problemsof overdependency and addiction, as well as from suicidal depression to disruptive ward behavior. Although the exactcause for postoperative psychosis has not been identified, medical and substance-induced mental disorders arecommonly diagnosed postoperatively in surgical patients. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;

107:458-461)

In oral and maxillofacial surgery, postoperative psy-chosis in previously healthy individuals has been infre-quently reported. Most such cases have occurred inpatients who have had a concomitant course of pro-longed or high dose of steroid therapy perioperatively.

We report a case of a 19-year-old female patient whodeveloped acute symptoms of psychosis following aminor surgical outpatient procedure and discuss thevarious predisposing factors with the possibility of asingle dose of dexamethasone being the most likelycause.

CASE REPORTA 19-year-old healthy woman reported to the Department

of Oral and Maxillofacial Surgery complaining of pain and

aProfessor, Department of Oral and Maxillofacial Surgery.bProfessor and Head, Department of Oral and Maxillofacial Surgery.cSenior Lecturer, Department of Oral and Maxillofacial Surgery.dAssistant Professor, Department of Psychiatry.eAssociate Professor, Department of Pharmacology.Received for publication Jun 12, 2008; returned for revision Dec 8,2008; accepted for publication Dec 16, 2008.1079-2104/$ - see front matter© 2009 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2008.12.027

458

pus discharge from an area around the last molar of the upperjaw on the left side. Medically, the patient was otherwisehealthy with no previous history of long-term medication orhospitalization.

Clinically, the patient had carious exposed first and secondmolars with evidence of an associated periapical cyst. End-odontic treatment of the involved teeth and enucleation of thecyst under local anesthesia was planned. Single-sitting rootcanal treatment for both molars was carried out one daybefore the surgery.

On the day of surgery, the patient was orally administered1 g amoxicillin and 400 mg ibuprofen 1 hour before surgery.She was also given a single dose of 8 mg dexamethasoneintravenously (equivalent to 54 mg prednisone) to reducepostoperative inflammation. Three milliliters of 2% ligno-caine hydrochloride with 1:80,000 adrenaline was then in-jected locally to achieve anesthesia, and enucleation of thecyst was carried out uneventfully. The procedure took ap-proximately 1 hour to complete, during which the patientremained calm and composed. She was advised to continuethe same antibiotics and analgesics for a total of 5 days.

On the third postoperative day, the parents of the patientobserved her to be laughing or crying without any apparentreasons. The patient was reassessed in the outpatient depart-ment and because she had no history of epilepsy, hallucina-tions, loss of consciousness, head injury, or high-grade fever

for long durations, a provisional diagnosis of postoperative

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psychosis was made. The patient was referred to the psychi-atry department for management.

The patient’s history was reviewed and the patient wassubjected to thorough psychiatric examination. Detailed psy-chologic evaluation revealed that the significant disorganiza-tion in the patient behavior was not preceded by any physicaltrauma (such as head injury), fever, psychotic substance use,seizure activity, vomiting, diarrhea, or any significant meta-bolic derangement. There was neither personal nor familyhistory of any thyroid or other endocrinal metabolic dysfunc-tion.

Because of the presence of significant disorganization inpersonality behavior and the absence of significant psycho-social stress or any primary or secondary gain (or any con-scious motive), the possibility of dissociative disorder ormalingering was ruled out.

During the initial mental status examination, the patientwas fully conscious and oriented to time, place, and person,thus excluding the possibility of delirium. She was alert butremained noncooperative; however, inappropriate affect wasobservable. No manic/depressive/first rank schneideriansymptoms could be elicited or observed. These, along withabsence of any personal or family history of mood disorderand schizophrenia, ruled out the possibility of these disorders.Her hematology and biochemistry results were unremarkable.A provisional diagnosis of steroid-induced psychosis wasmade, and the patient was prescribed lorazepam, 1 mg atnight once daily for a week.

On the seventh day, in addition to the problems she alreadyhad, the patient had visual and auditory hallucinations, com-plaining of seeing and hearing unknown people in her roomand behind doors, when actually no one was present. Risperi-done, 1 mg twice daily, was added to her previous medica-tions. The patient showed recovery from the next day onwardand by the 14th day after onset, no affective or psychoticsymptoms were observed or reported.

The patient continued to remained asymptomatic onweekly and then fortnightly evaluation. After 30 days ofmedication, the antipsychotic drugs were gradually taperedoff, because it was felt that the patient had stabilized to herpremorbid levels. No signs of recurrence of symptoms werenoted on subsequent visits.

DISCUSSIONA wide range of behavioral symptoms may occur

after surgery, including new-onset or recurrent depres-sion, hallucinations, true psychosis, mania, anxietysymptoms, impulsivity, and acute post-traumatic stressdisorder.1

Several causative factors have been identified whichcould predispose to postsurgical psychosis. These couldbe summarized as follows:

1. High fever.2. Electrolyte disturbances.3. Lack of sleep.2

4. Metabolic disturbance, e.g., hypoglycemia.

5. Emotional reaction to operation.

6. Withdrawal delirium in alcohol- or barbiturate-de-pendent individuals.

7. Postsurgical hyperthyroidism.3

Elderly medically compromised inpatients undergo-ing prolonged surgery under general anesthesia areespecially prone to develop psychiatric disturbancesdue to the above factors.

In the present case, there was no clinical or biochem-ical evidence of an organic cause for the psychoticreaction. The etiologic factor was therefore thought tobe one of the medications administered to the patient.Literature was searched for evidence of psychotic re-actions to the medications that our patient receivedperioperatively during her course of treatment.

1. Dexamethasone. Psychosis is one of the known,well documented, but poorly understood complica-tions of systemic steroid therapy. Most often, pa-tients receiving short-term corticosteroid therapypresent with euphoria or hypomania, whereas long-term therapy patients tend to present with depressivesymptoms.4

A single dose of intra-articular injection of 40 mgmethylprednisolone acetate has been reported to causepsychotic symptoms.5 Recently, a group of steroidsexclusively synthesized locally in the central nervoussystem (CNS), termed neurosteroids, have been discov-ered which have been implicated in modulating behav-ioral and CNS effects of corticosteroids.6

2. Amoxicillin. Psychotic symptoms are a recognizedcomplication of treatment with procaine penicillin;classic features of anxiety/panic and hallucinationshave been termed Hoigne syndrome. The likelycause seems to be a procaine-related effect on thelimbic system.7,8 There are rare reports of psychoticreactions occurring in patients being treated withamoxicillin. Presence of preexisting cerebrovasculardisease, hypoxia secondary to pneumonia, and mul-tiple drug therapy have been implicated as predis-posing factors in these cases.9-12

3. Ibuprofen. Nonsteroidal antiinflammatory drugs canexacerbate psychotic reactions in previously knownpsychiatric patients. The molecular mechanisms in-volved in ibuprofen-induced mental status changes areunclear but may be related to a direct effect on brainactivity or to an inhibitory effect on brain cyclooxy-genase, prostaglandins, and neurotransmitters.13-16

There has been little convincing evidence that psychi-atric side-effects are a major concern when prescribingamoxicillin.17 Ibuprofen has not been shown to producepsychosis in previously psychologically healthy patients.

Lignocaine (lidocaine) toxicity and adverse reaction to

OOOOE460 Bansal et al. April 2009

adrenaline (epinephrine) are mentioned for the sake ofcompletion but were highly unlikely, with psychotic man-ifestations occurring 3 days after their administration.Therefore, we believe that the postoperative psychosis inthe present patient was steroid induced. In maxillofacialsurgery, psychosis after short-term high-dose therapy withsteroids has been reported,18-20 but we are not aware ofany reports of severe psychosis arising after systemicadministration of a single dose of 8 mg dexamethasone ina healthy individual with no past psychiatric history.

Corticosteroids are a powerful therapeutic option,but they are also associated with serious adverse ef-fects, both physiologic and psychiatric. The somaticadverse effects of corticosteroid therapy have beenextensively researched and widely described.

The neuropsychiatric adverse effects, on the otherhand, have limited description, and the etiology andpathogenesis of these brain effects remain poorly un-derstood.

The potential psychiatric adverse effects of cortico-steroids span a symptom spectrum from subtle moodchanges to full-blown affective syndromes and frankpsychosis. Patients should also be evaluated for anysuggestion of suicidality. Braunig et al., in their studyof 150 cases of corticosteroid-induced psychosis, found26 patients with suicidality, including 15 with suicidalideation, 8 who attempted suicide, and 3 who com-pleted suicide.21

Warrington and Bostwick have stated that clinicallysignificant symptoms are those that disrupt patient’sdaily lives or cause distress to them or to those aroundthem.4 Mild to moderate reactions are those represent-ing changes in mood or behavior that do not reach thelevel of a diagnosable psychiatric disorder. The mostfrequently identified symptoms include agitation, anx-iety, distractibility, fear, hypomania, indifference, in-somnia, irritability, lethargy, labile mood, pressuredspeech, restlessness, and tearfulness. A severe reaction,on the other hand, is defined as “serious enough torequire psychiatric advice and treatment”.22 Thepresent patient reported hallucinations and extremevariations in mood which is considered to be a severereaction warranting treatment.

Among the various risk factors, the corticosteroiddosage is the most important risk factor for the devel-opment of psychiatric symptoms.4 The Boston Collab-orative Drug Surveillance Program monitored 676 con-secutive hospitalized patients who received prednisonetherapy and recorded a 1.3% (6 out of 463) incidence ofpsychiatric disturbances in patients receiving 40 mg/dor less, a 4.6% (8 out of 175) incidence in patientsreceiving 41-80 mg/d, and an 18.4% (7 out of 38)incidence in patients receiving �80 mg/d.23 However,

dose does not predict onset, severity, type, or duration

of symptoms.24,25 Neither previous corticosteroid-in-duced psychiatric disturbances nor previous treatmentfree of such disturbances predicts future responses totreatment. Likewise, a history of psychiatric illnessdoes not predict occurrence.26 No particular age groupappears to be at increased risk. Female patients have aminimally, but statistically significant, increased risk ofpsychiatric disturbances.27

As mentioned, even a single dose of intra-articularinjection of 40 mg methylprednisolone acetate has beenreported to cause psychotic symptoms.5 It is thereforeour contention that the present patient manifested psy-chotic symptoms due to the single injection of 8 mgdexamethasone given before surgery.

Psychiatric disturbances can occur at any point dur-ing corticosteroid treatment, including almost immedi-ately, after initiation, and even after cessation of treat-ment. However, most occur early in the therapeuticcourse.28

Management strategies for corticosteroid-inducedpsychiatric disturbances are based almost entirely oncase reports, anecdotal evidence, and a few small caseseries. Several open-label studies have evaluated pro-phylactic regimens for prevention of adverse psychiat-ric effects associated with long-term corticosteroidtreatment and reported successful use of lithium car-bonate,29 chlorpromazine,30 valproic acid,31 gabapen-tin,32 lamotrigine,33 and risperidone.34-36 For acute cor-ticosteroid-induced psychiatric disturbances, atypicalantipsychotics (eg, aripirazole, clozapine, olanzapine,olanzapine/fluoxetine, risperidone, quetiapine, ziprasi-done) generally appear to yield the greatest benefit withthe fewest adverse effects. Antidepressants have beenfound to help in some situations, but they exacerbateagitation and psychosis in others. Limited data suggesta role for antidepressants in depressed patients whorequire long-term corticosteroid administration.

Palliative pharmacotherapy is indicated for patientsin whom the corticosteroid cannot be stopped or re-duced, or who suddenly develop psychosis, severe ag-itation, aggressive behavior, or other intolerable symp-tom complexes.

In the present case, the initial treatment with loraz-epam was ineffective; the symptoms further increasedand the patient started hallucinating, which required theaddition of an atypical antipsychotic drug, risperidone.

Educating patients about potential adverse effectsand asking about the presence of such effects at eachpatient encounter can enhance early intervention foradverse corticosteroid-induced psychiatric reactions.

CONCLUSIONPostoperative psychosis occurring in a patient with

no known predisposing factors should be thoroughly

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investigated. A vast array of medications are known tocause psychosis in susceptible patients. Corticosteroidsare often implicated whenever they are given in highdoses or for long durations. However as this case reportsuggests, even a single prophylactic dose of dexameth-asone can precipitate psychotic reactions.

Neither dosage nor any other identified factor pre-dicts onset, duration, or severity of the psychiatricdisturbance. Most patients will recover fully with dosereduction or discontinuation of corticosteroid therapy.For those with symptoms of psychosis, aggression, oragitation, atypical antipsychotics should be first-linetherapy, with expected responses within a week. Allpatients who develop psychiatric disturbances whiletaking corticosteroids should be evaluated for suicidalideation at each physician/psychiatrist/maxillofacialsurgeon consultation. Therefore all patients undergoingmaxillofacial surgery who had been administered cor-ticosteroids whether preoperatively or postoperativelyshould be evaluated for steroid induced psychosis ifthey have one or more risk factors for psychosis.

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Reprint requests:

Dr. Vishal BansalOral and Maxillofacial SurgerySubharti Dental CollegeMeerut, Uttar Pradesh 250001India

drbansalvishal@rediffmail.com