Psychiatric Quarterly

, Volume 80, Issue 1, pp 23–40

Delirious Mania and Malignant Catatonia: A Report of 3 Cases and Review

Authors

    • Psychiatry ServiceVeterans Affairs Medical Center
    • Department of Psychiatry and Neurobehavioral SciencesThe University of Virginia
  • Abhishek Mehra
    • Carilion-University of Virginia Roanoke-Salem Psychiatric Medicine Residency ProgramUniversity of Virginia
  • Thomas Rowell
    • Carilion-University of Virginia Roanoke-Salem Psychiatric Medicine Residency ProgramUniversity of Virginia
  • Kye Y. Kim
    • Psychiatry ServiceVeterans Affairs Medical Center
    • Department of Psychiatry and Neurobehavioral SciencesThe University of Virginia
  • Geoffrey Bader
    • Psychiatry ServiceVeterans Affairs Medical Center
    • Department of Psychiatry and Neurobehavioral SciencesThe University of Virginia
Original Paper

DOI: 10.1007/s11126-009-9091-9

Cite this article as:
Detweiler, M.B., Mehra, A., Rowell, T. et al. Psychiatr Q (2009) 80: 23. doi:10.1007/s11126-009-9091-9

Abstract

Delirious mania is often difficult to distinguish from excited catatonia. While some authors consider delirious mania a subtype of catatonia, the distinction between the two entities is important as treatment differs and effects outcome. It appears that as catatonia is described as having non-malignant and malignant states, the same division of severity may also apply to delirious mania. Non-malignant delirious mania meets the criteria for mania and delirium without an underlying medical disorder. The patients are amnestic, may lose control of bowel and bladder, but still respond to atypical antipsychotics and mood stabilizers. However, with increasing progression of the disease course and perhaps with an increasing load of catatonic features, delirious mania may convert to a malignant catatonic state (malignant delirious mania) which is worsened by antipsychotics and requires a trial of benzodiazepines and/or ECT. Three case reports are presented to illustrate the diagnostic conundrum of delirious mania and several different presentations of malignant catatonia.

Keywords

Delirious maniaCatatoniaMalignant catatoniaNeuroleptic malignant syndromeAtypical antipsychotics

Introduction

The syndrome of delirious mania may often present with puzzling symptoms and etiologies that can delay appropriate and timely treatment, increasing the risk of mortality. The North American and voluminous international literature include a confounding variety of nomenclatures that began in 1832 with the first reported description of the syndrome by Calmeil in France in 1832 [1]. Delirious mania consists of a constellation of symptoms that can arise from both psychotic and affective psychiatric diseases as well and from many medical diseases [2]. It has been described as a subtype of the catatonia syndrome having a rapid onset with signs of mania, delirium and catatonia [24]. Manic signs include insomnia, acute excitement, grandiosity, emotional lability, delusions, altered consciousness, disorientation characterized by delirium often accompanied by posturing, stereotypy, mutism, negativism and echo-phenomena suggesting catatonia [2, 3]. An additional recently described symptom of delirious mania is pouring water over the head or on the floor [5].

In a case series of 16 delirious mania patients, Karmacharya et al. [5] summarized their patient demographics. Aside from two older outliers of 43 and 64 years of age, the average age was 21 years. Women (13/16) suffered more frequently than men. A majority (10/16) had prior histories of bipolar disorder and seven patients had histories of drug and alcohol abuse. Other prior diagnoses included depression (2/16), anxiety disorder (1/16), PTSD (1/16) and psychotic episode (1/16). Only one patient had no previous psychiatric history.

Luther Bell is acknowledged to be the first author in the North American literature to describe delirious mania [6]. Since that time the syndrome has had a confusing variety of names including: “acute delirious mania” [7]; “specific febrile delirium” [8], “delirium acutum” [911]; “manic-depressive psychosis” [12]; “benign stupors” [13]; “hyperactive or exhaustive mania” [14]; and “lethal catatonia” [15]. In the North American literature, Kraines [16] suggested that this syndrome be designated “Bell’s Mania” after Luther Bell. Despite the diversity of nomenclature in different countries, the delirious mania syndrome symptomatology has been fairly consistently described in the clinical reports [2]. There has been an increased discussion in the North American and International literature regarding the nosology of delirious mania and catatonia [2, 3, 1721].

Fink [2] has described delirious mania as “a syndrome of acute onset of excitement, grandiosity, emotional lability, delusions and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium. Almost all patients exhibited signs of catatonia”. Fink and Taylor [3] have published a concise and definitive discussion of the various clinical presentations of catatonia including delirious mania, NMS, serotonin syndrome, excited catatonia, and periodic catatonia in the effort to standardize the description and diagnosis of what are posited to be subtypes of a broad catatonic syndrome. They propose a new DSM classification of catatonia with 3 subtypes and four specifiers [21]. These authors emphasize that the multiple presentations of catatonia need to be delineated for both clinical and neuroscience research ends. The critical objective of their nomenclature proposal is the rapid diagnosis and treatment of delirious mania and catatonia to prevent syndrome progression from reaching a malignant state where mortality risk is increased.

The syndrome of catatonia featuring a cyclic mixture of mood and motor signs was first described in 1874 by Kahlbaum [22, 23]. Fink [2] reported that approximately 6%–9% of new inpatient psychiatric admissions exhibit catatonic features. Some studies suggest that 7.6%–40% of catatonias are idiopathic while approximately 14% of catatonias are secondary to a general medical condition [614, 16, 2022]. Recently, there have been more reports of catatonia associated with mood disorders than with schizophrenias [23]. The development of catatonia rating scales [2426] has improved clinical recognition [2]. Three or more signs on the Peralta et al. [25] catatonia diagnostic scale have a sensitivity of 100% and a specificity of 99% [23]. Catatonia can be broadly divided into two variants, excited-delirious and retarded-stuporous [20]. The principal signs of catatonia include mutism, stupor, negativism (Gegenhalten), posturing (catalepsy), waxy flexibility, stereotypy, automatic obedience, echopraxia, echolalia, and mannerisms [2]. Over 40 catatonic phenomena have been identified in the literature [20, 27]. Some authors suggest that the presence of any two signs of catatonia for 24 h or more justifies the diagnosis of catatonia [28, 29].

In the past and in DSM III, catatonia was principally associated with schizophrenia, despite reports of catatonia being associated with mood disorders (e.g., depression, bipolar disorder) and medical maladies (e.g., infections, toxic states) [2, 30]. Like delirious mania, catatonia may be non-malignant or malignant [2, 23, 31]. Malignant catatonia differs from non-malignant catatonia with the former exhibiting autonomic instability consisting of an elevated fever (>38°C), tachycardia and hypertension. Speech and thoughts are disorganized, accompanied by intense excitement, cataplexy, mutism, rigidity, stereotypy and posturing. This syndrome has also been referred to as Bell’s Mania and delirious mania due to overlapping symptoms [2].

We present three cases of catatonia to illustrate the similarities and differences in the varied subtypes including non-malignant delirious mania, malignant catatonia associated with schizophrenia and a case of catatonia secondary to varying medical etiologies that evolved into two other catatonia forms. The clinical features of each case are described according to the criteria of DSM IV TR, Peralta et al. [25] and Fink and Taylor [3].

Case Reports

Case 1

Mr X is 47-year-old male with no former psychiatric history who was transferred to our hospital after recent admissions at two other hospitals where he had presented with insomnia, sexual disinhibition, liability, and generally disorganized behavior accompanied by neglected hygiene, inappropriate behavior and paranoid thoughts. He was reported to have stopped taking his mediations following discharge from the first hospital.

Prior to the recent hospitalizations, the patient was described as being exceptionally hardworking, preoccupied with his health, for example taking his blood pressure multiple times a day. His concern about body fat contributed to daily runs of 12 to 15 miles, while working two shifts at work and getting an estimated 1–2 h of sleep per night. Family and friends had noticed an increasing trend of hyperactivity with increasing confused and disinhibited speech. His family also reported his activities to include, working 27 straight days, working two shifts daily, daily long runs while averaging 1 h of sleep per night plus non stop volunteering to help church families. He had no history of drug or tobacco use.

On the acute psychiatry ward, the patient demonstrated extreme fluctuations of mood and cognition with visual hallucinations resulting in behavior of plucking “flying insects” and objects out of the air and off the walls and furniture. Periods of agitation included pushing staff, pounding on doors and demanding to be released. When conversant he showed no insight about his recent past or present situations, cognition or functional state. Despite autonomic instability with elevated temperature (37.8°C/100.04°F), pulse (93), respirations (24) and reported pain (10/10), his physical examination was non focal. Electrocardiogram (EKG) and chest X-ray were unremarkable. Normal laboratory results included TSH, CBC, PT/PTT, Troponin I, hepatitis C, RPR and urinalysis. Abnormal labs included mildly decreased serum protein (5.8 g/dl), serum albumin (3.0 g/dl) alkaline phosphatase (32 U/l) and RBC (4.48 × 106/μl) with a marginally increased SGOT (43 μ/l). The urine drug screen was negative, the serum alcohol level and GGT were normal.

After admission he tried to elope and required sedation and physical restraints. His delirious state was marked by grimacing and motoric agitation including disrobing, removing the mattress from his bed and crawling on the floor. In addition to the visual hallucinations he appeared to be responding to auditory hallucinations. He would march around his bed, alternating with sitting on the bed while performing repetitive hand movements as if performing a manual task. Speech ranged from mute to delusional ramblings. Staff initiated questions were often met with echolalia during the several days of acute mania with delirium. He lost bowel and bladder control requiring diapers for several days. His CLOX test and MMSE were zero as the patient could not participate and was oriented to person only.

Intake medications included levetiracetam 50 mg twice daily, citalopram 40 mg once daily and ziprasidone 60 mg twice daily. Levetiracetam was stopped, citalopram was held due to the mania, ziprasidone 60 mg twice a day was continued and olanzapine 20 mg was added for mood stabilization and psychosis. Haloperidol and lorazepam were ordered on an as needed basis. On day three the patient had decreased disorganized behavior and a taper of the ziprasidone was started. Increased confusion and disorganization followed this. The ziprasidone dose was returned to 60 mg twice a day and olanzapine was increased to 30 mg at night. On day seven the delirium had subsided, however the patient was amnestic to his symptoms and behavior for the week of delirium in the hospital and for at least one week prior to admission.

The patient gradually improved with a stepwise decreased agitation and catatonic symptoms. By day 12, cognition had markedly improved (CLOX1 = 13/15, CLOX2 = 11/15, MMSE = 30/30). The patient became depressed when hearing about his activities during the manic and delirious episodes, worrying about losing his job, marriage and respect in his church community. Citalopram was restarted for depression. Lamotrigine 25 mg daily was initiated for bipolar depression and titrated to 50 mg bid. Ziprasidone was cross tapered to quetiapine 150 mg twice a day for psychosis and olanzapine 30 mg qhs was continued. He was also referred for marital and job counselling. The patient left the acute service and his care was transferred to the outpatient service at another hospital. There have been no additional episodes of acute mixed mania with catatonia (delirious mania) for the past 4 years, with present medications including aripiprazole 10 mg and venlafaxine HCL 75 mg daily.

Case 2

A 62-year-old male with a 40 year history of paranoid schizophrenia was transferred to our acute inpatient service as a result of him kicking a hole in a hospital wall and threatening to kill the staff at another hospital where he had been admitted for acute exacerbation of paranoid schizophrenia. He had been committed, placed in restraints and transferred. The patient had started showing signs of mania, insomnia, hypersexuality and aggression several months prior to his admission following the death of one of his daughters and with the subsequent assumption of care of her five children.

On admission he had a reduced hemoglobin of 9.0 (baseline 12.5 g/dl) and a positive hemoccult. He was admitted to the step-down unit for hypotension and to rule out a lower GI bleed. The patient became verbally abusive and threatening to the staff resulting in being placed in 4-point restraints. He was deemed inappropriate for colonoscopy, was considered hemodynamically stable and he was transferred to psychiatry.

On transfer to the acute psychiatric unit the patient attempted to assault the officer who escorted him to the ward. He was largely incoherent, not redirectable and demonstrated severe psychomotor agitation. He had marked sexual disinhibition including verbal aggression towards female staff, plus disrobing and masturbation when not in restraints. He exhibited inappropriate and bizarre postures with grimacing and guttural vocalizations. At times he was mute aside from making the guttural sounds. His level of aggression required continual restraints. Intake laboratory abnormal values included albumin (2.4 g/dl), protein (5.8 g/dl), iron (23 μg/dl), RBC (3.86 × 106/μl), hemoglobin (9.0 g/dl), hematocrit (27.5%), platelets (407/mm [3]), magnesium (2.8 mEq/l), Westergren (36 mm/h). Temperature increased to 38°C (100.4°F), pulse to 116, and blood pressure to 178/56. Chest X-ray was normal and the head CT demonstrated no changes incongruent with the patient’s age.

The patient refused to take any oral medications, food or fluids. He was started on scheduled intramuscular olanzapine. Daily olanzapine doses exceeding 40 mg a day and intramuscular diazepam, with doses up to 125 mg a day, had no effect in controlling the delirium. With increasing CPK (high 1714.0 U/l), thought to be principally due to his agitation in restraints, in addition to increasing WBC (12.8 × 106/μl) with minimal fluid and food intake, he was transferred to the ICU for intravenous medications, fluids and nutrition. He failed intramuscular haloperidol and benzodiazepines, therefore, these were discontinued and ECT was initiated on day 12. With each ECT there was a direct decrease in motoric and verbal agitation in addition to increased compliance with fluids, food and medications. He was transferred back to the acute psychiatric unit midway through the ECT course. He was restarted on olanzapine which was titrated to 20 mg at night and he returned to his quiet, courteous baseline with no overt signs of mood or psychotic symptoms. The patient was found to have underlying cognitive impairment (MMSE 11/30, CLOX1 3/15, CLOX2 13/15). The patient was discharged on omeprazole for GERD and olanzapine 20 mg at night. An out patient colonoscopy was scheduled at primary care clinic. It was recommended that he be followed in a memory disorders clinic. After 3 years, the patient remains on the olanzapine 20 mg and he has had no acute episodes of schizophrenia with excited catatonia (malignant catatonia).

Case 3

A 61-year-old female with a history of bipolar disorder, diabetes mellitus type II, hypertension, hyperlipidemia, hypothyroidism and gastroesophageal reflux was admitted to the ER for right arm pain. It was reported that she had stopped taking her trifluoperazine for an indeterminate time prior to admission and she had been having increasing falls. She was also prescribed escitalopram and lithium. The patient was found to have an elevated troponin I and elevated creatinine kinase. She also presented with slurred speech and altered mental status described as “pleasantly demented”. Significant positive signs included elevated blood pressure (174/80), temperature (37.8°C), pulse (100 bpm), and respirations (20). Oxygen saturation was 94% on room air, there was a grade II systolic murmur at the left base, bilateral +1 pitting edema and marked ecchymoses. An extended bladder contained one liter of urine. EKG showed nonspecific ST wave changes. Head CT and chest X-ray were noncontributory. Her lithium level was 0.64 mEq/l. Significant laboratory values included increased WBC (15.3 × 106/μl), AST (127 U/l), ALT (61 U/l) and decreased sodium (129 mEq/l). The patient was restarted on trifluoperazine 25 mg, lithium 225 mg in the morning and 450 mg in the evening. Haloperidol 1 mg IV every 4 h was ordered for agitation. Mental status waxed and waned with periods of unresponsiveness. EEG showed slowing secondary to muscle tension. Temperatures reached 38.3°C and an LP done on day 5 showed one WBC/μl, 17 RBC/μl and a protein of 32 mg/dl. CSF cryptococcal antigen was negatives and the CSF VDRL was nonreactive. Transesophageal echocardiography revealed aortiosclerosis, mild left ventricular hypertrophy, a 0.8 × 0.4 cm left ventricular calcification and a calcified left aortic valve.

One week after admission, the patient was incoherent, had cogwheel and nuchal rigidity and a head MRI revealed small vessel disease. Trifluoperazine was discontinued and the olanzapine was started, however, the patient continued to demonstrate dysarthria and psychotic symptoms. Ziprazidone 80 mg twice a day was added on day nine with lithium continued. On day 10 the patient was still incoherent with her eyes closed. The olanzapine and ziprazidone were stopped and replaced with trifluoperazine 5 mg in the morning and 20 mg in the evening. Haloperidol 2 mg every 4 h was ordered for agitation. Lithium was continued. On day 11 the patient became unable to recognize her long term psychiatrist. She was disoriented, incoherent, physically and verbally agitated, exhibiting negativism by refusing to follow commands or open her eyes. Significant rigidity was noted. Suspecting NMS the trifluoperazine and lithium were discontinued. Urinalysis showed an E. coli infections and ceftriaxone 1 mg/24 h was initiated. When blood cultures were positive for coagulase positive Staphylococcus, vancomycin 1250 mg was given. White blood cell count remained in the 10–15 (×106/μl) range throughout the hospitalization.

Antibiotic therapy ended on day 21, however, patient’s clinical condition continued to deteriorate with the patient becoming unable to take oral food or fluids. The patient developed a significant hypokalemia which was stabilized by day 28. The patient remained in a delirious state and unable to feed or hydrate herself. Intravenous hydration was continued and ECT was initiated on day 28. There was a gradual improvement in mental status and with slow resumption of oral fluids, food and medications. A total of six ECT sessions were employed. As the patient had a history of poor response to atypical antipsychotics, she was discharged on haloperidol 10 mg at night, escitalopram 10 mg daily and benztropine 1 mg three times a day.

Discussion

The three cases all meet criteria for delirious mania and catatonia according to Fink [2] (Table 1), in addition to meeting DSM IV TR criteria for schizophrenia catatonic type (295.20) and for the mood disorders with catatonia features specifier (Table 2). Moreover, the three cases also meet catatonia criteria according to Peralta et al. [25] (Table 3). The first two cases meet criteria for DSM IV TR delirium criteria due to a general medical condition without having an identified contributing general medical condition (Table 4). The third case had underlying medical conditions on hospital admission, thus meeting DSM IV TR criteria for delirium due to a general medical condition (293.0) (Table 4). These three cases represent patients frequently seen in ERs and on medical and acute psychiatric units. There are two fundamental questions for the clinician. First what is the correct diagnosis and second what is the appropriate treatment?
Table 1

Catatonia subgroups delirious mania and catatonia [3]

Symptoms

Delirious mania

Symptoms

Catatoniaa

Case 1

Case 2

Case 3

Case 1

Case 2

Case 3

Sudden onset

X

X

X

Acute onset of excitement

X

X

X

Intense excitement

X

X

X

Grandiosity

 

X

 

Hyperthermia

 

X

 

Emotional lability

  

X

Catalepsy

  

X

Delusions

X

X

 

Mutism

X

X

X

Insomnia of mania

X

X

 

Rigidity

  

X

Disorientation

X

X

X

Stereotypy

X

X

X

Altered consciousness

X

X

X

Posturing

 

X

 

Negativism

X

X

X

Tachycardia

X

X

X

Stereotypy

X

X

X

Tachypnea

X

X

X

Posturing

X

X

 

Hypertension

 

X

X

Pressured Speech and Mutism

X

X

X

Disorganized thoughts

X

X

X

Flight of Ideas

   

Disorganized speech

X

X

X

Hyperthermia

X

X

X

Refuse food and fluids

X

X

X

Tachycardia

X

X

X

Cycle from excited state to stuporous state

  

X

Tachypnea

X

X

X

    

Hypertension

 

X

X

aRequires 2 or more signs for 24 h or longer (See Ref. [3])

Table 2

Criteria for schizophrenia catatonic type (295.20); mood disorders with catatonia features specifier (DSM IV TR)

Symptoms

Case 1

Case 2

Case 3

Motoric immobility

   

Waxy flexibility

   

Stupor

  

X

Excessive motor activity

X

X

X

Extreme negativism

   

Rigidity

  

X

Mutism

X

X

X

Peculiarities of involuntary movement

   

Inappropriate postures

X

X

X

Bizarre postures

 

X

 

Prominent grimacing

X

X

X

Echolalia

X

  

Echopraxia

   
Table 3

Catatonia diagnostic criteria [25]a

Symptom (11 most sensitive signs)

Case 1

Case 2

Case 3

Immobility/stupor

  

X

Mutism

X

X

X

Negativism

X

X

X

Opposition

X

X

X

Posturing

X

X

 

Catalepsy

  

X

Automatic obedience

   

Echo phenomena

X

  

Rigidity

  

X

Verbigeration

 

X

X

Withdrawal/refusal to eat or drink

X

X

X

aRequires 3 or more for positive diagnosis

Table 4

Delirium due to a general medical condition (293.0) (DSM IV TR)

Symptoms

Case 1

Case 2

Case 3

Disturbance of consciousness

X

X

X

↓ awareness of environment

X

X

X

↓ ability to focus

X

X

X

↓ ability to sustain attention

X

X

X

↓ ability to shift attention

   

Change in cognition

X

X

X

Memory deficit

X

X

X

Disorientation

X

X

X

Language disturbance

X

X

X

Perceptual disturbance

   

Short onset

X

X

 

Daily fluctuating course

   

Evidence of a General medical condition

  

X

Differential Diagnosis

Medical Etiology Rule Outs

The differential diagnosis of both delirium and catatonia may include head injury, seizures, metabolic disorders, medication intoxication (NMS, serotonin syndrome), exacerbations of medical conditions, mood disorders and psychotic disorders [4]. In the medical setting, delirium from toxicity or withdrawal from recreational drugs (benzodiazepines, cocaine, amphetamines, barbiturates, etc.) and alcohol are frequent findings and need to be ruled out with appropriate history and laboratory tests. This is especially important in the psychiatric setting considering the comorbidity of drug and alcohol use in patients with psychiatric disorders [30]. Bowl and bladder incontinence as in case 1 is not a common clinical finding other than in profound cognitive deterioration such as in moderate to severe dementia [32], or in delirious mania with marked cognitive disorientation [2, 30].

In these case reports, the patient in case 3 presented in the ER with slurred speech, right should and right arm pain, recent falls, hyperthermia (38.9°C), autonomic instability (BP 174/80), a systolic grade 2 murmur, disorientation, agitation, ongoing UTI, pulmonary hypertension on CXR and small vessel disease on head MRI. She had significantly altered blood chemistries including AST (127 U/l), ALT ((61 U/l), WBC (15.3 × 106 /μ), CK-MB (52 U/l), troponin (0.48 ng/dl), BUN (32 mg/dl), creatinine (11.3 mg/dl), glucose (327 mg/dl), low serum sodium (129 mEq/l) with an EKG showing a non-specific ST change. The patient had also stopped taking her conventional antipsychotic and lithium. Thus, the role of a multiple destabilizing general medical conditions needs to be investigated and a delirium of mixed etiologies, more probably to general medical conditions, should be considered at first presentation in the emergency room.

In case 3, after first presenting in an agitated state, the patient’s behavior was subsequently described as having episodes of waxing and waning mental status unresponsive to medications, accompanied by temperatures of 38.4–38.9°C and by periods of unresponsiveness or stupor. On some examinations she would moan and she was reported to be unaware of her examiners. A UTI with gram positive clusters was treated with ceftriaxone. When blood cultures were positive, suggesting septicemia, and vancomycin was started. This suggests that the poorly controlled diabetes mellitus may have altered the patient’s immune response leading to a concurrent local and then a systemic infection. It can be argued that the patient’s failure to take her antipsychotic and mood stabilizer contributed to not taking her medications for diabetes and hypertension. Thus, case 3 appears to be initiated by a delirium secondary to hyperglycemia, hypertension with progressing local and systemic infections compounded by medication noncompliance.

Delirious Mania vs Other Forms of Catatonia

Once identified as probably not having an organic etiology, the diagnosis of delirious mania versus another form of catatonia is the next step. The first question is whether the presenting symptoms were predominantly delirious or catatonic (Tables 1, 2 and 3)? In the DSM IV TR, delirium is attributed to states resulting from medical conditions or substance use. Delirium is not recognized as being associated with either schizophrenia or mood disorders. Catatonia on the other hand, has both states of motoric immobility and states of excessive motor activity. Catatonic features may appear during an episode of delirium [2]. According to DSM IV TR criteria, catatonic features may also accompany schizophrenia or a mood disorder. If the predominant features were those of delirium with minor catatonic features, the diagnosis would probably be delirious mania. This does not imply that the catatonic features will remain minor compared to the delirious mania features as the disease progresses and perhaps become predominant as in case 3.

Delirious mania has no DSM IV TR or ICD classification. Until the classification scheme of Fink and Taylor [3], delirious mania was considered by many to be an acute exacerbation of bipolar disorder as it has responded to antipsychotics and mood stabilizer therapy in some reports [33]. Clinicians are aware that whenever there are clinical signs of delirium and catatonia in the presence of antipsychotics, serotonergic agents and multiple psychiatric medications, NMS should also be included the differential diagnosis [2, 20].

Both cases 1 and 2 meet DSM IV TR criteria for delirium due to a medical condition without having an identifiable acute medical condition. All 3 cases meet criteria for delirious mania (Table 1) and catatonia according to the DSM IV TR (Table 2) in addition to the catatonia criteria of Peralta et al. [25] (Table 3). Both patients in cases 1 and 2 first presented with elevated mood, grandiosity and disinhibition. As stated above, patient 3 was initially agitated with slurred speech on admission, however, she lapsed into episodes of stuporous catatonia. The cluster of catatonic signs seems to have increased as the disease course progressed in all three cases.

Non-Malignant vs Malignant Catatonia

The next step is to differentiate between non-malignant and malignant catatonia as this distinction guides treatment. As a result of the development and implementation of standardized examinations and rating scales, catatonia has been more frequently documented to be associated with affective disorders and neurotoxic states [2, 33]. Exhibiting a notable diversity of symptoms including motoric signs, excitement or stupor, bizarre and repetitious behavior, it has been suggested that in the absence of autonomic instability and hyperthermia, the catatonia be termed “simple or non-malignant catatonia”. In the presence of autonomic instability and hyperthermia, the syndrome becomes “malignant catatonia” [18, 28, 34]. Taylor and Fink [20] suggest that the nonmalignant forms of catatonia be referred to as the Kahlbaum syndrome.

In case 1, a 47-year-old male with no prior psychiatric history until the events that lead to his three consecutive hospitalizations. By his third admission, he presented with predominantly delirious symptoms and he exhibited progressing catatonic symptoms as the delirium worsened. There was mild hyperthermia (37.8°C) and mild autonomic instability. Notably, the patient responded to atypical antipsychotics and mood stabilizers which generally are not effective in cases of malignant catatonia [2, 31]. These factors suggest that the threshold for malignant delirious mania/catatonia was not reached in this case.

In case 2, a 62-year-old male with a history of paranoid schizophrenia, presented with signs of mania, insomnia, hypersexuality, aggression and delirium accompanied by extreme excitation, hyperthermia (38°C, more significant in an older patient) and with moderate autonomic instability. He refused food and liquids during the excited phase requiring continual 4-point restraints and required several sessions of intravenous hydration. He was unresponsive to atypical antipsychotics and benzodiazepines and only responded to ECT. These clinical characteristics would qualify the case as a malignant form of delirious mania or malignant catatonia.

The patient in case 3 entered the hospital in an agitated state with hyperthermia and autonomic instability seemingly from several medical conditions (acute sub staphylococcal coagulase negative infection, acute E. coli UTI, electrolyte imbalance, hypertensive cardiovascular disease). As the medical problems were resolved, the patient continued to have signs of delirium and stupor unresolved with the reintroduction of her outpatient trifluoperazine and lithium. She improved marginally on olanzapine and ziprazidone, but she had some residual dysarthria and psychosis. Change to trifluoperazine, lithium and haloperidol as a PRN produced increased agitation, disorientation, muscular rigidity and amnesia. At this stage the diagnosis of NMS could be considered. However, it probably was not the initial etiology of the malignant catatonia, rather a result of treatment employing a rapidly changing regimen of conventional and atypical antipsychotics, in addition to lithium. NMS has been associated with trifluoperazine [35], trifluoperazine with lithium [36], lithium and haloperidol [37], ziprazidone [38], ziprazidone and lithium [39], olanzapine [40], and olanzapine and lithium [41]. Regardless of the initial etiology in this case, the disease course progressed from delirium due to a several general medical conditions, to NMS and finally to malignant catatonia.

DSM IV TR vs Fink and Taylor Classifications

Diagnostic clarity is difficult for the clinician who sees only several cases of delirious mania, exited catatonia or malignant catatonia each year. This is compounded by some confusion in the literature secondary to authors using a diversity of competing classification schemes [2, 20, 21]. Diagnostic clarity may be further confounded by the DSM IV TR classification as the clinician will not find an appropriate code for “delirious mania” or “malignant catatonia” with either an apparent organic or functional etiology. Taylor and Fink [20, 21] have presented a thorough discussion of the DSM IV TR limitations and their suggestions for a new catatonia classification system. With the present DSM IV TR system, delirious mania (case 1) or malignant catatonia (case 2) associated with psychotic or affective disorder could be diagnosed as a mood disorder with catatonic features (DSM IV TR page 417) and schizophrenia catatonic type (DSM IV TR 295.20) respectively. Catatonia due to general medical conditions would be acceptable for phase one of case 3 as the patient was not taking her antipsychotics or mood stabilizer and had numerous active medical problems on admission. During phase two of her disease course, she was being started and stopped on multiple antipsychotics combined with lithium and haloperidol PRN, which may have initiated a NMS syndrome. In an early stage, the NMS would be probably be classified as a drug induced form of non-malignant catatonia by Fink and Taylor [3]. With increasing switching of conventional and atypical antipsychotics, in addition to lithium, the NMS became malignant, which would be classified as a drug induced form of malignant catatonia by Fink and Taylor [3]. DSM IV TR makes no distinction between the non-malignant and malignant stages of NMS.

When delirious mania is diagnosed, the differential diagnosis would include delirious mania versus excited catatonia, excited catatonia versus catatonia dominated by inhibition, mania with psychotic features versus delirious mania and catatonia versus NMS [2]. Also, the question for all the possibilities, is whether the presenting disease state is a non-malignant or malignant form? The predominance of evidence supporting catatonia, delirium or NMS may be the deciding factor. If there is a predominating cluster of signs supporting either delirium or catatonia, this may be the deciding diagnostic element. NMS would be suspected if the catatonic signs followed the introduction of an antipsychotic. Or, the diagnosis may depend on when the disease was first observed. Evidence of the preceding phase or phases may not be available to the treating clinician.

In case 1, the delirious mania was the patient’s first psychiatric episode and could be classified as a mood disorder with catatonic features using DSM IV TR. However, this does not indicate the difference between a nonmalignant and malignant episode. The delirium does not qualify for the DSM IV TR diagnosis of delirium as there is no underlying medical condition. The proposed DSM addition by Fink and Taylor of catatonia as a separate entity with subtypes (nonmalignant, delirious and malignant) in addition to 4 specifiers (mood disorders, general medical conditions or toxic states, neurological disorders, psychotic disorders) [21] would classify case 1 as delirious catatonia secondary to a mood disorder.

In case 2, the delirious mania or excited catatonia that progressed to a malignant state was associated with a re-exacerbation of paranoid schizophrenia. DSM IV TR would classify this as schizophrenia catatonic type. As in case 1, there is no qualifier for nonmalignant or malignant catatonia. Employing the Fink and Taylor diagnostic suggestions [21], case 2 would be labeled as malignant catatonia secondary to a psychotic disorder.

In case 3, the patient seems to have had the initial symptoms of delirium secondary to underlying medical conditions at intake, resulting from the patient failing to take her medications for hypertension and diabetes with eventual infections. This could be classified by DSM IV TR criteria as a “delirium due to general medical condition (poorly controlled diabetes, hypertension and with urinary tract and eventually systemic infections). However, more appropriately, as there is a delirious mania accompanying the medical conditions, a more appropriate DSM IV TR diagnosis would be “catatonic disorder due to a general medical illness” (DSM IV TR 293.89). It would not meet criteria for DSM IV TR “mood disorder with catatonic features” as the medical problems were more prominent in contributing to the delirium than the bipolar symptoms at admission. This does not discount the signs of catatonia. Also, none of these diagnoses account for the signs of non-malignant catatonia versus malignant catatonia. With progression of the disease and the resolution of the initial medical problems, the patient appears to have entered into a delirious mania that was treated with a multitude of medications (conventional and atypical antipsychotics were added to lithium) that eventually precipitated a NMS state which subsequently progressed to malignant catatonia.

Depending on the classification criteria, case 3 in the early phase could be classified as having delirious catatonia due to general medical conditions [21], or delirium secondary to general medical conditions (DSM IV TR), or catatonia [25]. The second phase could be diagnosed as NMS in either the non-malignant or malignant form depending on the day of illness, with a final presentation of malignant catatonia. Fink and Taylor [21] probably would have classified phase 2 as non-malignant catatonia due to a toxic state (NMS), and finally malignant catatonia due to a toxic state (NMS) in the final phase. In the third phase DSM IV TR would have described the clinical presentation as NMS or bipolar disorder with catatonic features.

In such complex cases as case 3, it can be observed that an initially nonmalignant syndrome can rapidly progress to malignant catatonia having both signs of organic and functional impairment. If the clinician does not have a thorough understanding of delirious mania/excited catatonia and malignant catatonia, the reported etiology may reflect the clinician’s orientation [5]. The diagnosis may also be missed as earlier treatment of the delirious mania and malignant catatonia syndromes may reduce the number of cases in which a case of nonmalignant catatonia progresses to the stuporous phase. It has been suggested that the earlier treatment in recent years has resulted in the failure to recognize an underlying catatonic syndrome in many more cases since the advent of ECT in 1934. Regardless of the initial etiology, once fully developed, malignant delirious mania and malignant catatonia syndromes have a high mortality if appropriate treatment is delayed [2, 17, 19, 31].

Treatment

Historical

Perhaps the most critical clinical question is whether the delirious mania or catatonia is non-malignant or malignant [2, 31]. Prior to the introduction of ECT in 1934, over 80% of persons afflicted with delirious mania (or delirious catatonia) died in hours to days following stuporous exhaustion, coma and cardiovascular collapse [17, 19]. In Bell’s historic review of 1700 admissions to his hospital from 1836–1849, 75% of the 40 patients identified as having delirious mania died [2, 6]. In the early neuroleptic era, medications were largely ineffective once the delirious mania and nonmalignant catatonia progressed to malignant forms [4244]. A few authors reported the success of utilizing ACTH and corticosteroids in the early 1940s [45, 46], however, some cases also employed ECT in addition to the corticosteroids thus improving treatment efficacy [17, 47]. The treatment of choice in 1980 was a combination of haloperidol and lithium [33]. The use of neuroleptics for malignant catatonic syndromes is still rarely effective [1719, 48].

The advent of ECT markedly improved prognosis. Early reports describe treatment with an average of 25–40 ECT sessions with an extreme case requiring 200 sessions [17]. One technique, the “shock block” technique, employed three to five ECT sessions with 15 min intervals followed by three more during the following 12 h [17, 49]. Improved and earlier diagnosis with support from intravenous fluids reduced the number of ECT sessions to two to 14 daily bilateral sessions [2, 3, 17, 50, 51]. It is notable that one form of catatonia has been reported to have a familial link [5254] that portends a poor prognosis as it seems to respond poorly to benzodiazepines and ECT [20].

Treatment for Non-Malignant Delirious Mania/Catatonia

It may be prudent to initiate treatment for delirious mania while continuing a medical work-up. If one utilizes the nosological system of Fink and Taylor [3, 21] delirious mania is a variant of catatonia. Thus, it follows that some authors suggest that benzodiazepines are the first treatment choice regardless of phase [2, 3, 20, 48, 55]. However, case reports and retrospective studies have shown that there are alternative and perhaps second line treatments for the non-malignant stages of some of the catatonic variants. For non-malignant catatonic schizophrenia, atypical antipsychotics and mood stabilizers have proven effective [31, 33, 56]. In a review of 16 cases of delirious mania Karmacharya el al. [5] identified clozapine, olanzapine and quetiapine as effective atypicals. Ziprasidone was successfully employed in case 1. Successful mood stabilizers have included lithium, valproate and oxcarbazepine [5].

The non-malignant stages of delirious mania may correspond to Kraeplin’s [57] “manic-depressive psychosis” that had a less severe course, including a lower fever, insomnia, shorter duration, hypomania or mania and delusions. The malignant phase of delirious mania appears similar to Kraeplin’s “collapse delirium” with a high fiver, confusion, flight of ideas, extreme excitement and hallucinations.

Atypical antipsychotics were effective in case 1, congruent with the retrospective studies and case reports cited by Van Den Eede et al. [31] in their discussion of the use of antipsychotics for nonmalignant catatonia. In case 1, the patient responded to two atypical antipsychotics with mood stabilizing properties (ziprasidone, olanzapine). Tapering the ziprasidone made the symptoms worse. If the symptoms are primarily secondary to a medication induced toxic states (e.g., NMS), then stopping the medications should improve the symptoms [56, 58].

Treatment for Malignant Delirious Mania/Catatonia

Benzodiazepines

If delirious mania evolves into malignant catatonia, use of neuroleptics are ineffective and should be discontinued [2, 31, 44]. In this situation, the only treatment modalities recommended by most authors are benzodiazepines or ECT with use of conventional or atypical neuroleptics only worsening the disease course [2, 31, 44, 48]. The malignant patient may have a high fever, tachycardia, elevated blood pressure and be dehydrated if not having received continuous intravenous fluids as in cases 2 and 3. While ECT is the most frequently reported curative measure both in the pre-neuroleptic and neuroleptic eras [2, 19, 31, 42, 59, 60] a new early benzodiazepine early intervention has been proposed [55].

Some authors suggest using benzodiazepines in both non-malignant and malignant states of delirious mania and catatonia. Lorazepam 6–20 mg/day appear to be effective up to a certain malignant threshold, after which ECT is more effective [30]. Bush et al. [48] employed a 5-day oral or parenteral benzodiazepine challenge (1 mg given every 5 min for two doses, maximum 8 mg/day) with reduction in symptoms as measured by Bush-Francis Catatonia Rating Scale (BFCRS) [24]. The greater the drop in BSCRS scores on the first day following the second lorazepam dose, the better the response to the benzodiazepine.

It is notable that American Psychiatric Association recommends that benzodiazepines be avoided in cases of delirium. With the current understanding of delirious mania, this guideline may need modification for the treatment of delirious mania [5]. Effective benzodiazepine dosing has been reported for delirious mania in a pediatric patient [61], for idiopathic catatonia [62] and for catatonia associated with schizophrenia [55].

Pommepuy and Januel [23] have proposed a five step treatment protocol for catatonia which would also include delirious mania: (1) stop medication(s) suspected of symptom production; (2) test for and treat underlying physical disease states (include standard chemistries, urine drug screen, EEG, head CT); (3) trial of lorazepam 2.5 mg; rate catatonic signs after 1 h; with partial or total response, start 3 mg/for 6 days followed by a tapering dose; (4) for the 20% that may not respond to lorazepam, employ ECT; if malignant catatonia is suspected by the presence of and/or autonomic instability go directly to ECT.

Huang [55] reported a 100% response rate on day one when the patients were treated with lorazepam 2 to 4 mg im. If the response is not sufficient, intravenous diazepam 10 mg/2 m/l in 500 m/l is infused with normal saline every 8 h. Other authors have not reported success with benzodiazepine use once the disease progresses to malignant catatonia. When the delirious mania progressed to a malignant phase, lorazepam doses as high has 10 mg/day have failed [2] as did a midazolam drip of 8 mg/h [44]. If the delirious mania progresses to a malignant phase, ECT may need to be employed as it has been reported to be effective in reducing mortality regardless of the etiology of the syndrome [2, 19, 31, 44].

ECT

Most cases of malignant delirious mania have responded to ECT and it is the consensus treatment of choice with the majority of malignant cases requiring two-12 ECT sessions [2, 5, 31, 44]. Some authors recommend every other day ECT [44], while others suggest daily ECT treatments to hasten recovery [2, 3]. A more conservative ECT protocol than “shock block” [49], is the “en bloc” ECT regimen consisting of daily ECT on two or more consecutive days. In the 13 cases of malignant catatonia cited by Philbrick and Rummons [18], six of the eight patients receiving ECT survived. Karmacharya et al. [5] in their retrospective series of 16 delirious mania cases reported that the last effective treatment in 10 cases was high dose benzodiazepines (4 cases), lithium and valproate (2 cases) and clozapine (2 cases). In six cases ECT was the last effective treatment choice with clinical improvement noted after one to four ECT sessions.

We propose that delirious mania (or delirious catatonia) may have a less acute stage that responds to mood stabilizers and antipsychotics in addition to benzodiazepines as suggested by Van Den Eede et al. [31] and as illustrated in the cases series of Karmacharya et al. [5]. However, like other forms of malignant catatonia, once the threshold is reached for severe malignant delirious mania (or malignant catatonia), benzodiazepines or ECT are the treatment of choice. The malignant phase of delirious mania may be identified by having a predominance of catatonic signs as opposed to the nonmalignant phase of delirious mania when delirium signs predominate. These phases can be documented by employing serial catatonia rating scale [24, 25] scores during the disease course. As the clinician observes increases in catatonic signs, the suspicion of an impending progression into a malignant state should be expected. Once malignant catatonia is suspected, failure to respond to benzodiazepines with a concurrent continued increase in catatonic signs might be an index of having breached the malignancy threshold. Thus, we suggest that delirious mania, like other forms of catatonia, can be divided into non-malignant and malignant forms. These nonmalignant forms seem to be responsive to atypical antipsychotics and mood stabilizers, which are not effective in the malignant catatonic stage. A limitation of atypical antipsychotics and mood stabilizers is that they may not resolve the non-malignant symptoms as rapidly as benzodiazepines and mood stabilizers [5].

Conclusions

Delirious mania and excited catatonia are often difficult to distinguish. More than 25% of manic patients have catatonic features and meet criteria for catatonia. Also, more than 50% of catatonic patient have features of mania. Delirious mania seems to be a more acute form of mania that will respond to antipsychotics and mood stabilizers in the nonmalignant stage, but not when it has progressed to malignant delirious mania. Delirious mania patients may have catatonic features that increase with disease progression. It is unclear if the threshold for converting from non-malignant delirious mania to malignant delirious mania is quantitative, based on the number of catatonic features as measured by appropriate scales and/or on quantitative thresholds for hyperthermia and autonomic instability. The possibility of quantifiable thresholds for the conversion from non-malignant delirious mania to malignant delirious manic (or malignant catatonia) would benefit from future studies. This delineation might be helpful to clinicians in assuring appropriate treatment and it might reduce the risk of progression from non-malignant to malignant delirious mania syndromes as classified by Fink and Taylor [3, 21]. By aiding the clinician in achieving an early diagnosis and appropriate treatment, the prognosis of delirious mania may be improved.

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© Springer Science+Business Media, LLC 2009