Can anticholinergics like benztropine be used to treat Catatonia?

Can anticholinergics like benztropine be used to treat Catatonia?

We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

I found an old paper describing a case study where a catatonic patient was successfully treated with benztropine (Cogentin). However, I can't find any modern guidelines that calls for this treatment (first-line is usually benzodiazepams). Is there any reason not to use anticholinergics for catatonia treatment?


  1. Albucher RC, DeQuardo J, Tandon R. Treatment of catatonia with an anticholinergic agent. Biol Psychiatry. 1991;29(5):513-514. doi:10.1016/0006-3223(91)90281-p
  2. Francis A. Catatonia: diagnosis, classification, and treatment. Curr Psychiatry Rep 2010; 12:180.

Anticholinergics by themselves commonly have sedative effects. The reason you read about benztropine being used is that it has dopaminergic activity as well (in addition to anticholinergic activity). Specifically, benztropine and its derivatives are also dopamine reuptake inhibitors.

So from the perspective that benztropine is a dopamine reuptake inhibitor, i.e. a stimulant in the traditional sense, it would probably be a bad idea to use as a treatment for catatonia. If I remember right, its particular binding affinity is significant at the dopamine transporter.

A Comprehensive List of Anticholinergic Drugs

Here’s a comprehensive list of Anticholinergic Drugs. This list is courtesy of The People’s Pharmacy and was included in Dr. Shelly Gray’s study at the University of Washington:

  • Amitriptyline (Elavil)
  • Atropine
  • Benztropine (Cogentin)
  • Chlorpheniramine (Actifed, Allergy & Congestion Relief, Chlor-Trimeton, Codeprex, Efidac-24 Chlorpheniramine, etc.)
  • Chlorpromazine (Thorazine)
  • Clomipramine (Anafranil)
  • Clozapine (Clozaril)
  • Cyclobenzaprine (Amrix, Fexmid, Flexeril)
  • Cyproheptadine (Periactin)
  • Desipramine (Norpramin)
  • Dexchlorpheniramine
  • Dicyclomine (Bentyl)
  • Diphenhydramine (Advil PM, Aleve PM, Bayer PM, Benadryl, Excedrin PM, Nytol, Simply Sleep, Sominex, Tylenol PM, Unisom, etc.)
  • Doxepin (Adapin, Silenor, Sinequan)
  • Fesoterodine (Toviaz)
  • Hydroxyzine (Atarax, Vistaril)
  • Hyoscyamine (Anaspaz, Levbid, Levsin, Levsinex, NuLev)
  • Imipramine (Tofranil)
  • Meclizine (Antivert, Bonine)
  • Nortriptyline (Pamelor)
  • Olanzapine (Zyprexa)
  • Orphenadrine (Norflex)
  • Oxybutynin (Ditropan, Oxytrol)
  • Paroxetine (Brisdelle, Paxil)
  • Perphenazine (Trilafon)
  • Prochlorperazine (Compazine)
  • Promethazine (Phenergan)
  • Protriptyline (Vivactil)
  • Pseudoephedrine HCl/Triprolidine HCl (Aprodine)
  • Scopolamine (Transderm Scop)
  • Thioridazine (Mellaril)
  • Tolterodine (Detrol)
  • Trifluoperazine (Stelazine)
  • Trimipramine (Surmontil)

• *Tissue responses to large doses of cholinergic agonists.

Direct-Acting Cholinergic Agonists: Many drugs classified as direct-acting cholinergic agonists are primarily selective to the muscarinic receptors but are nonspecific because the muscarinic receptors are located in the smooth muscle of the GI and genitourinary tracts, glands, and heart.  Metoclopramide hydrochloride (HCl) is a direct-acting cholinergic agonist that is usually prescribed to treat gastroparesis, nausea, and gastroesophageal reflux disease (GERD). In low doses, metoclopramide enhances gastric motility and thus accelerates gastric emptying time.  Bethanechol chloride, a direct-acting cholinergic agonist, acts on the muscarinic (cholinergic) receptor and is used primarily to increase urination in the treatment of urinary retention and neurogenic bladder. Pharmacokinetics of bethanechol: poorly absorbed from the GI tract. half-life is unknown. drug is most likely excreted in the urine. Pharmacodynamics promote micturition by stimulating the muscarinic cholinergic receptors in the detrusor muscle to contract the bladder and produce urine output. The patient voids approximately 30 minutes to 1.5 hours after taking an oral dose of bethanechol because of the increased tone of the detrusor muscle. Bethanechol also increases peristalsis in the GI tract. The drug should be taken on an empty stomach. It should not be administered by injection.

Direct-Acting Cholinergic: Eye: Pilocarpine (eye drop) is a direct-acting cholinergic agonist that constricts the pupils of the eyes, thus opening the canal of Schlemm to promote drainage of aqueous humor (fluid). This drug is used to treat glaucoma by relieving fluid (intraocular) pressure in the eye and to promote miosis in eye surgery and examinations. An oral form of pilocarpine is used to relieve xerostomia (dry mouth). Pilocarpine also acts on the nicotinic receptor.

NURSING PROCESS: Cholinergic Agonist, Direct Acting: Bethanechol (Urecholine) Assessment

  • Assess baseline vital signs for future comparison.
  • Assess urine output (should be &gt1500 mL/d).
  • Obtain patient history of health problems such as peptic ulcer, urinary obstruction, or asthma. Cholinergic agonists can aggravate symptoms of these conditions.
  • Impaired urinary elimination related to urinary retention
  • Anxiety related to wheezing
  • Risk for impaired skin integrity related to rash
  • Ineffective breathing pattern related to excess mucous secretions in lungs
  • Monitor patient’s vital signs. Heart rate and blood pressure decrease when large doses of cholinergic are taken. Orthostatic
  • hypotension is a side effect of a cholinergic agonist such as bethanechol.
  • Record fluid intake and output. Decreased urinary output should be reported because it may be related to urinary obstruction.
  • Give cholinergic agonists 1 hour before or 2 hours after meals. If patient complains of gastric pain, the drug may be given with meals.
  • Check serum amylase, lipase, aspartate aminotransferase, and bilirubin levels. These laboratory values may increase slightly when taking cholinergic agonists.
  • Observe patient for side effects such as gastric pain or cramping, diarrhea, increased salivary or bronchial secretions, bradycardia, and orthostatic hypotension.
  • Auscultate breath sounds for rales (cracking sounds from fluid congestion in lungs) or rhonchi (rough sounds resulting from mucous secretions in lungs). Cholinergic agonists can increase bronchial secretions.


The frequency of catatonia in the general population is difficult to assess and is thought to be underrecognized ( 79 ). A study evaluating patients admitted to an inpatient psychiatric service receiving Bush-Francis Rating scales (N=201) had a prevalence of catatonia of 9.45% with no difference in rate or symptom profile, depending on underlying psychotic versus affective disorder ( 54 ).

In 261 cases in the world literature, medical conditions associated with catatonia included structural neurologic lesion (74%), illicit or therapeutic drug toxicity (17%), and metabolic encephalopathy (9%) ( 26 ) (Table 2). In a prospective analysis of 138 consecutive admissions to a psychiatric hospital, 16 (11%) of the patients were found to have 2 or more symptoms of catatonia, with all but 1 responding to lorazepam ( 127 ).

Recognition of catatonia is enhanced with psychiatric consultation whereas patients with features of echolalia, grimacing, and agitation were more likely to be underdiagnosed with catatonia despite meeting criteria ( 79 ).

Nonpharmacological Therapies

Goals for the treatment of schizophrenia include identifying symptoms, increasing functioning, and preventing relapse. Typically, pharmacological and non-pharmacological treatments are combined in order to help improve daily functioning and symptom management, each of them targeting their own symptoms and areas of functioning. For example, medications are used to reduce positive and sometimes negative symptoms or to manage side effects while psychotherapeutic approaches aim to improve coping skills, symptom management, daily functioning, socialization, and the ability to work and manage one’s own life. Consider the typical age of onset for schizophrenia, for example. It usually manifests in the early years of adulthood as the brain finishing maturing. Thus, the disorder often interferes directly with learning and maintaining vital skills for autonomy and living, including managing finances, establishing relationships and families, living on one’s own, finding work and a career, and many more essential skills. Psychotherapeutic approaches seek to teach or re-teach coping and illness management skills and other skills of daily living and include cognitive enhancement therapy, individual, and group therapy.

Even a brief yet major psychotic episode can be highly disruptive to the livelihood and functioning of an individual and his/her family and friends. Psychotherapeutic management would involve medically informing the patient and his or her family about the condition and treatment modalities employed for the particular patient. Along with emphasizing reintegration into the societal milieu, it is essential to focus on managing comorbid disorders or stressors and improving overall coping skills. These therapies can be delivered in both individual and group settings once the person’s active symptoms have been stabilized.

In individual treatment, the person is the focus of the treatment and has all the attention and interaction with the therapist insight-oriented therapies often are not effective if the person has ongoing symptoms since abstract thinking and planning are significantly impaired some forms of individual therapy may be helpful if a person achieves significant remission. A group setting, although time and focus is divided, can be a beneficial form of therapy as individuals often can find support and comfort in hearing the stories of individuals with similar experiences and form friendships based on healing and a deep understanding.

Other support services for education, employment, and housing are usually offered for those with schizophrenia. For people suffering from severe schizophrenia and discharged from a stay in the hospital, these services are often brought together in an integrated approach to offer support in the community away from the hospital setting. In addition to medicine management, housing, and finances, assistance is given for more routine matters such as help with shopping and using public transportation. This approach is known as assertive community treatment (ACT) and has been shown to achieve positive results in symptoms, social functioning, and quality of life. Another more intense approach is known as intensive care management (ICM). Intensive care management (ICM) is a stage further than assertive community treatment (ACT) and emphasizes support of high intensity in smaller caseloads, (less than twenty). This approach is to provide long-term care in the community. Studies show that intensive care management (ICM) improves many of the relevant outcomes including social functioning.

Cognitive-Behavioral Therapy

In long-term psychoses and schizophrenia, CBT is used to complement medication and is adapted to meet individual needs. Interventions particularly related to these conditions include exploring reality testing (evaluating one’s own thinking and beliefs to see how well they match the actual environment), changing delusions and hallucinations, examining factors that precipitate relapse (particularly related to stress, interpersonal conflicts, and treatment resistance), and managing relapses. While several meta-analyses suggested that CBT is effective in schizophrenia, other studies contradict these findings. [5]

Link to Learning

Cognitive Enhancement Therapy (CET)

The evidence that cognitive deficits also contribute to functional impairment in schizophrenia has led to an increased search for treatments that might enhance cognitive function in schizophrenia. Unfortunately, as of yet, there are no pharmacological treatments that work consistently to improve cognition in schizophrenia, though many new types of drugs are currently under exploration. However, there is a type of psychological intervention, referred to as cognitive remediation, which has shown some evidence of boosting cognitive functioning in schizophrenia.

In particular, a version of this treatment called cognitive enhancement therapy (CET) has been shown to improve cognition, functional outcome, social cognition, and protection against gray matter loss (Eack et al., 2009 Eack, Greenwald, Hogarty, & Keshavan, 2010 Eack et al., 2010 Eack, Pogue-Geile, Greenwald, Hogarty, & Keshavan, 2010 Hogarty, Greenwald, & Eack, 2006) in young individuals with schizophrenia. The treatment was designed for persons whose positive and negative symptoms have been stabilized but who still struggle to function well socially and vocationally. It works by having individuals participate in structured group and computer-based exercises, with the goal of improving socialization skills and cognitive functioning (e.g., mental stamina and information processing). [6] The development of new treatments such as cognitive enhancement therapy (CET) provides some hope that we will be able to develop new and better approaches to improving the lives of individuals with this serious mental health condition and potentially even prevent it someday.

Watch IT

In this video, Juno mentions a little bit about his experiences with schizophrenia and why he chooses not to take medications.

Third-wave-approaches are new developments in CBT that emphasize the importance of acceptance, mindfulness, and emotions, the therapeutic relationship, values, goals, and meta‐cognition (Hayes & Hofmann, 2017). In psychosis, adaptations of mindfulness-based therapy, acceptance and commitment therapy (ACT) and compassion-focused therapy (CFT) have been studied most. In order to ease distress and achieve acceptance as well as to support the regaining of control, mindfulness-based interventions for psychosis guide patients to notice sensations and their own emotional and cognitive reactions to them with awareness (Chadwick, 2014). In meditation-based practices, patients learn to observe their thoughts, feelings, and symptoms in an accepting and non-judgmental way. Mindfulness interventions for psychosis have been implemented as single treatments (e.g. Chadwick, 2014) or combined with CBT (e.g. Wright et al., 2014).

In acceptance and commitment therapy (ACT) (Hayes, Strosahl, & Wilson, 1999), experiential avoidance (avoiding one’s feelings or avoiding taking productive actions) and cognitive fusion (having behavior driven by one’s thoughts without questioning the validity of one’s assumptions or beliefs) are suggested to be the core processes of suffering. In order to increase psychological flexibility and reduce distress associated with psychotic symptoms, patients are guided to develop a balance between committed value-guided action when solving actual problems and acceptance when control of thoughts and feelings is limited (e.g., in the case of hallucinations). Acceptance and commitment therapy (ACT) has been adapted for the treatment of psychosis (O’Donoghue, Morris, Oliver, Johns, & Hayes, 2018 combined with CBT, Wright et al., 2014).

Compassion-focused therapy (CFT) (Gilbert & Procter, 2006) encourages patients to be more compassionate towards themselves and others while reducing shame and self-criticism. Compassionate mind training includes appreciation and imagery exercises as well as aspects of mindfulness and aids the patient to experience different aspects of compassion in order to promote mental wellbeing. Compassion-focused therapy (CFT) has also been adapted for the treatment of psychosis (Brähler, Harper, & Gilbert, 2013).

Metacognitive training (MCT) (Moritz & Woodward, 2007) was designed to address positive symptoms in patients with schizophrenia. As cognitive biases have been related to positive symptoms (e.g., jumping to conclusions or externalizing attributional bias—assuming the motivations of others, see Garety & Freeman, 1999), metacognitive training (MCT) aims to extend the patient’s knowledge of cognitive biases and to provide corrective experiences. Implementing a wide range of examples and exercises, patients participating in metacognitive training (MCT) group training are encouraged to identify and gain insight into these cognitive biases and reduce conviction in delusional ideas. MCT is mainly administered in group format.

Social skills training (SST) builds on the observation that patients with psychotic disorders tend to show impaired social skills. Social skills training (SST) involve therapist modeling and instructing socially confident behavior in specific situations combined with role plays. Patients receive supportive feedback from the therapist and video feedback can also be used. During the end of the training that usually takes place in group format, patients are encouraged to practice the newly learned skills in daily life. [7]

Try It


cognitive enhancement therapy (CET): therapy shown to improve cognition, functional outcome, and social cognition and to protect against gray matter loss


Benzatropine is used to reduce extrapyramidal side effects of antipsychotic treatment. Benzatropine is also a second-line drug for the treatment of Parkinson's disease. It improves tremor, and may alleviate rigidity and bradykinesia. [9] Benzatropine is also sometimes used for the treatment of dystonia, a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.

These are principally anticholinergic:

While some studies suggest that use of anticholinergics increases the risk of tardive dyskinesia (a long-term side effect of antipsychotics), [10] [11] other studies have found no association between anticholinergic exposure and risk of developing tardive dyskinesia, [12] although symptoms may be worsened. [13]

Drugs that decrease cholinergic transmission may impair storage of new information into long-term memory. Anticholinergic agents can also impair time perception. [14]

Benzatropine is a centrally acting anticholinergic/antihistamine agent. It is a selective M1 muscarinic acetylcholine receptor antagonist. Benzatropine partially blocks cholinergic activity in the basal ganglia and has also been shown to increase the availability of dopamine by blocking its reuptake and storage in central sites, and as a result, increasing dopaminergic activity. Animal studies have indicated that anticholinergic activity of benzatropine is approximately one-half that of atropine, while its antihistamine activity approaches that of mepyramine. Its anticholinergic effects have been established as therapeutically significant in the management of Parkinsonism. Benzatropine antagonizes the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early Parkinson's disease. [15]

Benzatropine analogues are atypical dopamine reuptake inhibitors, [16] which might make them useful for people with akathisia secondary to antipsychotic therapy. [17]

Benzatropine has been also identified, by a high throughput screening approach, as a potent differentiating agent for oligodendrocytes, possibly working through M1 and M3 muscarinic receptors. In preclinical models for multiple sclerosis, benzatropine decreased clinical symptoms and enhanced re-myelination. [19]

In veterinary medicine, benzatropine is used to treat priapism in stallions. [20]

Since 1959, benzatropine is the official international nonproprietary name of the medication under the INN scheme, the medication naming system coordinated by the World Health Organization it is also the British Approved Name (BAN) given in the British Pharmacopoeia, [1] [2] and has been the official nonproprietary name in Australia since 2015. [21] Regional variations of the "a" spelling are also used in French, Italian, Portuguese, and Spanish, as well as Latin (all medications are assigned a Latin name by WHO). [2]

"Benztropine" is the official United States Adopted Name (USAN), the medication naming system coordinated by the USAN Council, co-sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USP), and the American Pharmacists Association (APhA). It is also the Japanese Accepted Name (JAN) [22] and was used in Australia until 2015, when it was harmonized with the INN. [21]

Both names may be modified to account for the methanesulfonate salt as which the medication is formulated: the modified INN (INNm) and BAN (BANM) is benzatropine mesilate, while the modified USAN is benztropine mesylate. [23] The modified JAN is a hybrid form, benztropine mesilate. [22]

The misspelling benzotropine is also occasionally seen in the literature.

Unintended Anticholinergic Effects

On the other hand, there are drugs that have an unintended anticholinergic effect. They include certain antidepressants and antipsychotics which increase or decrease dopamine and serotonin neurotransmitters to alter a person’s mood. In some cases, the drugs can block acetylcholine and lead to anticholinergic side effects.

The challenge, of course, is that antidepressants and antipsychotics are often prescribed over the long term, making the management of symptoms all the more difficult.


Antidepressants and antipsychotics with anticholinergic effects include:

  • Elavil (amitriptyline)
  • Norpramin (desipramine)
  • Tofranil (imipramine)
  • Pamelor (nortriptyline)
  • Paxil (paroxetine)
  • Thorazine (chlorpromazine)
  • Clozaril (clozapine)
  • Zyprexa (olanzapine)
  • Mellaril (thioridazine)

In between both of these extremes, there are times when low-dose antidepressants can be used to treat chronic pain and IBS. A similar effect is achieved with certain low-dose antipsychotics and Parkinson's disease.  

By weighing the pros and cons of the anticholinergic effect, doctors can find the right drug and dosage by which to deliver treatment without the burden of side effects.

A Word From Verywell

If you are experiencing intolerable side effects due to the anticholinergic effects of a drug, speak with your doctor. Depending on your condition, the doctor may be able to decrease the dosage or find the appropriate substitution.

However, you should not discontinue any drug without first speaking with your doctor. Doing so can sometimes cause ill effects (especially with certain antidepressants) unless treatment is gradually tapered off.

Use only as directed. Tell your doctor if you use other medicines or have other medical conditions or allergies.

You should not use Cogentin if you are allergic to it.

Not approved for use by anyone younger than 3 years old.

Tell your doctor if you have ever had:

Older adults may be more sensitive to the effects of Cogentin.

It is not known if Cogentin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

Tell your doctor if you are breastfeeding.

Catatonia: How to identify and treat it: Features that overlap with other syndromes make the diagnosis easy to overlook.

Is catatonia a rare condition that belongs in the history books, or is it more prevalent than we think? If we think we don't see it often, how will we recognize it? And how do we treat it? This article reviews the evolution of our understanding of the phenomenology and therapy of this interesting and complex condition.

In 1874, Kahlbaum (1,2) was the first to propose a syndrome of motor dysfunction characterized by mutism, immobility, staring gaze, negativism, stereotyped behavior, waxy flexibility, and verbal stereotypies that he called catatonia. Kahlbaum conceptualized catatonia as a distinct disorder, (3) but Kraepelin reformulated it as a feature of dementia praecox. (4) Although Bleuler felt that catatonia could occur in other psychiatric disorders and in normal people, (4) he also included catatonia as a marker of schizophrenia, where it remained from DSM-I through DSM-IV. (3) As was believed to be true of schizophrenia, Kraepelin considered catatonia to be characterized by poor prognosis, whereas Bleuler eliminated poor prognosis as a criterion for catatonia. (3)

In DSM-IV, catatonia was still a subtype of schizophrenia, but for the first time it was expanded diagnostically to become both a specifier in mood disorders, and a syndrome resulting from a general medical condition. (5,6) In DSM-5, catatonic schizophrenia was deleted, and catatonia became a specifier for 10 disorders, including schizophrenia, mood disorders, and general medical conditions. (3,5-9) In ICD-10, however, catatonia is still associated primarily with schizophrenia. (10)

A wide range of presentations

Catatonia is a cyclical syndrome characterized by alterations in motor, behavioral, and vocal signs occurring in the context of medical, neurologic, and psychiatric disorders. (8) The most common features are immobility, waxy flexibility, stupor, mutism, negativism, echolalia, echopraxia, peculiarities of voluntary movement, and rigidity. (7,11) Features of catatonia that have been repeatedly described through the years are summarized in Table 1 (8,12,13) (page 19). In general, presentations of catatonia are not specific to any psychiatric or medical etiology. (13,14)

Catatonia often is described along a continuum from retarded/stuporous to excited, (14,15) and from benign to malignant. (13) Examples of these ranges of presentation include (5,12,13,15-19):

Stuporous/retarded catatonia (Kahlbaum syndrome) is a primarily negative syndrome in which stupor, mutism, negativism, obsessional slowness, and posturing predominate. Akinetic mutism and coma vigil are sometimes considered to be types of stuporous catatonia, as occasionally are locked-in syndrome and abulia caused by anterior cingulate lesions.

Excited catatonia (hyperkinetic variant, Bell' s mania, oneirophrenia, oneroid state/ syndrome, catatonia raptus) is characterized by agitation, combativeness, verbigeration, stereotypies, grimacing, and echo phenomena (echopraxia and echolalia).

Malignant (lethal) catatonia consists of catatonia accompanied by excitement, stupor, altered level of consciousness, catalepsy, hyperthermia, and autonomic instability with tachycardia, tachypnea, hypertension, and labile blood pressure. Autonomic dysregulation, fever, rhabdomyolysis, and acute renal failure can be causes of morbidity and mortality. Neuroleptic malignant syndrome (NMS)--which is associated with dopamine antagonists, especially antipsychotics--is considered a form of malignant catatonia and has a mortality rate of 10% to 20%. Signs of NMS include muscle rigidity, fever, diaphoresis, rigor, altered consciousness, mutism, tachycardia, hypertension, leukocytosis, and laboratory evidence of muscle damage. Serotonin syndrome can be difficult to distinguish from malignant catatonia, but it is usually not associated with waxy flexibility and rigidity.

Several specific subtypes of catatonia that may exist anywhere along dimensions of activity and severity also have been described:

Periodic catatonia. In 1908, Kraepelin described a form of periodic catatonia, with rapid shifts from excitement to stupor. (4) Later, Gjessing described periodic catatonia in schizophrenia and reported success treating it with high doses of thyroid hormone. (4) Today, periodic catatonia refers to the rapid onset of recurrent, brief hypokinetic or hyperkinetic episodes lasting 4 to 10 days and recurring during the course of weeks to years. Patients often are asymptomatic between episodes except for grimacing, stereotypies, and negativism later in the course. (13,15) At least some forms of periodic catatonia are familial, (4) with autosomal dominant transmission possibly linked to chromosome 15q15. (13)

A familial form of catatonia has been described that has a poor response to standard therapies (benzodiazepines and electroconvulsive therapy [ECT]), but in view of the high comorbidity of catatonia and bipolar disorder, it is difficult to determine whether this is a separate condition, or a group of patients with bipolar disorder. (5)

Late (ie, late-onset) catatonia is well described in the Japanese literature. (10) Reported primarily in women without a known medical illness or brain disorder, late catatonia begins with prodromal hypochondriacal or depressive symptoms during a stressful situation, followed by unprovoked anxiety and agitation. Some patients develop hallucinations, delusions, and recurrent excitement, along with anxiety and agitation. The next stage involves typical catatonic features (mainly excitement, retardation, negativism, and autonomic disturbance), progressing to stupor, mutism, verbal stereotypies, and negativism, including refusal of food. Most patients have residual symptoms following improvement. A few cases have been noted to remit with ECT, with relapse when treatment was discontinued. Late catatonia has been thought to be associated with late-onset schizophrenia or bipolar disorder, or to be an independent entity.

Untreated catatonia can have serious medical complications, including deep vein thrombosis, pulmonary embolism, aspiration pneumonia, infection, metabolic disorders, decubitus ulcers, malnutrition, dehydration, contractures, thrombosis, urinary retention, rhabdomyolysis, acute renal failure, sepsis, disseminated intravascular coagulation, and cardiac arrest. (11,12,16,20,21) Mortality approaches 10%. (12) In children and adolescents, catatonia increases the risk of premature death (including by suicide) 60-fold. (22)

Not as rare as you might think

With the shift from inpatient to outpatient care driven by deinstitutionalization, longitudinal close observation became less common, and clinicians got the impression that the dramatic catatonia that was common in the hospital had become rare. (3) The impression that catatonia was unimportant was strengthened by expanding industry promotion of antipsychotic medications while ignoring catatonia, for which the industry had no specific treatment. (3) With recent research, however, catatonia has been reported in 7% to 38% of adult psychiatric patients, including 9% to 25% of inpatients, 20% to 25% of patients with mania, (3,5) and 20% of patients with major depressive episodes. (7) Catatonia has been noted in .6% to 18% of adolescent psychiatric inpatients (especially in communication and social disorders programs), (5,8,22) some children, (5) and 6% to 18% of adult and juvenile patients with autism spectrum disorder (ASD). (23) In the medical setting, catatonia occurs in 12% to 37% of patients with delirium, (8,14,17,18,20,24) 7% to 45% of medically ill patients, including those with no psychiatric history, (12,13) and 4% of ICU patients. (12) Several substances have been linked to catatonia these are discussed later. (11) Contrary to earlier impressions, catatonia is more common in mood disorders, particularly mixed bipolar disorder, especially mania, (5) than in schizophrenia. (7,8,17,25)

Conditions associated with catatonia have different features that act through a final common pathway, (7) possibly related to the neurobiology of an extreme fear response called tonic immobility that has been conserved through evolution. (8) This mechanism may be mediated by decreased dopamine signaling in basal ganglia, orbitofrontal, and limbic systems, including the hypothalamus and basal forebrain. (3,17,20) Subcortical reduction of dopaminergic neurotransmission appears to be related to reduced [GABA.sub.A] receptor signaling and dysfunction of N-methyl-D-aspartate (NMDA) receptors with glutaminergic excess in striato-cortical or frontal cortico-cortical systems. (13,20,26,27)

Up to one-quarter of cases of catatonia are secondary to medical (mostly neurologic) factors or substances. (15) Table 2 (5,13,15) (page 20) lists common medical and neurological causes. Medications and substances known to cause catatonia are noted in Table 3. (5,8,13,16,26)

Catatonia can be a specifier, or a separate condition

DSM-5 criteria for catatonia are summarized in Table 4. (28) With these features, catatonia can be a specifier for depressive, bipolar, or psychotic disorders a complication of a medical disorder or another separate diagnosis. (8) The diagnosis of catatonia in DSM-5 is made when the clinical picture is dominated by [greater than or equal to] 3 of the following core features (8,15):

* motoric immobility as evidenced by catalepsy (including waxy flexibility) or stupor

* excessive purposeless motor activity that is not influenced by external stimuli

* extreme negativism or mutism

* peculiarities of voluntary movement such as posturing, stereotyped movements, prominent mannerisms, or prominent grimacing

DSM-5 criteria for the diagnosis of catatonia are more restrictive than DSM-IV criteria. As a result, they exclude a significant number of patients who would be considered catatonic in other systems. (29) For example, DSM-5 criteria do not include common features noted in Table 1 (8,12,13) (page 19), such as rigidity and staring. (14,29) If the diagnosis is not obvious, it might be suspected in the presence of >1 of posturing, automatic obedience, or waxy flexibility, or >2 of echopraxia/echolalia, gegenhalten, negativism, mitgehen, or stereotypy/vergiberation. (12) Clues to catatonia that are not included in formal diagnostic systems and are easily confused with features of psychosis include whispered or robotic speech, uncharacteristic foreign accent, tiptoe walking, hopping, rituals, and odd mannerisms. (5)

There are several catatonia rating scales containing between 14 and 40 items that are useful in diagnosing and following treatment response in catatonia (Table 5, (8,13,15,29) page 22). Of these, the Kanner Scale is primarily applied in neuropsychiatric settings, while the Bush-Francis Catatonia Rating Scale (BFCRS) has had the most widespread use. The BFCRS consists of 23 items, the first 14 of which are used as a screening instrument. It requires 2 of its first 14 items to diagnose catatonia, while DSM-5 requires 3 of 12 signs. (29) If the diagnosis remains in doubt, a benzodiazepine agonist test can be instructive. (9,12) The presence of catatonia is suggested by significant improvement, ideally assessed prospectively by improvement of BFCRS scores, shortly after administration of a single dose of 1 to 2 mg lorazepam or 5 mg diazepam IV, or 10 mg Zolpidem orally. Further evaluation generally consists of a careful medical and psychiatric histories of patient and family, review of all medications, history of substance use with toxicology as indicated, physical examination focusing on autonomic dysregulation, examination for delirium, and laboratory tests as suggested by the history and examination that may include complete blood count, creatine kinase, serum iron, blood urea nitrogen, electrolytes, creatinine, prolactin, anti-NMDA antibodies, thyroid function tests, serology, metabolic panel, human immunodeficiency virus testing, EEG, and neuroimaging. (8,15,16)

A complex differential diagnosis

Manifestations of numerous psychiatric and neurologic disorders can mimic or be identical to those of catatonia. The differential diagnosis is complicated by the fact that some of these disorders can cause catatonia, which is then masked by the primary disorder some disorders (eg, NMS) are forms of catatonia. Table 6 (5,8,12,19,26,30) lists conditions to consider.

Some of these conditions warrant discussion. ASD may have catatonia-like features such as echolalia, echopraxia, excitement, combativeness, grimacing, mutism, logorrhea, verbigeration, catalepsy, mannerisms, rigidity, staring and withdrawal. (8) Catatonia may also be a stage of deterioration of autism, in which case it is characterized by increases in slowness of movement and speech, reliance on physical or verbal prompting from others, passivity, and lack of motivation. (23) At the same time, catatonic features such as mutism, stereotypic speech, repetitive behavior, echolalia, posturing, mannerisms, purposeless agitation, and rigidity in catatonia can be misinterpreted as signs of ASD. (8) Catatonia should be suspected as a complication of longstanding ASD in the presence of a consistent, marked change in motor behavior, such as immobility, decreased speech, stupor, excitement, or mixtures or alternations of stupor and excitement. (8) Freezing while doing something, difficulty crossing lines, or uncharacteristic persistence of a particular behavior may also herald the presence of catatonia with ASD. (8)

Catatonia caused by a neurologic or metabolic factor or a substance can be difficult to distinguish from delirium complicated by catatonia. Delirium may be identified in patients with catatonia by the presence of a waxing and waning level of consciousness (vs fluctuating behavior in catatonia) and slowing of the EEG. (12,15) Antipsychotic medications can improve delirium but worsen catatonia, while benzodiazepines can improve catatonia but worsen delirium.

Among other neurologic syndromes that can be confused with catatonia, locked-in syndrome consists of total immobility except for vertical extraocular movements and blinking. In this state, patients attempt to communicate with their eyes, while catatonic patients do not try to communicate. There is no response to a lorazepam challenge test. Stiff man syndrome is associated with painful spasms precipitated by touch, noise, or emotional stimuli. Baclofen can resolve stiff man syndrome, but it can induce catatonia. Paratonia refers to generalized increased motor tone that is idiopathic, or associated with neurodegeneration, encephalopathy, or medications. The only motor sign is increased tone, and other signs of catatonia are absent. Catatonia is usually associated with some motor behaviors and interaction with the environment, even if it is negative, while the coma vigil patient is completely unresponsive. Frontotemporal dementia is progressive, while catatonia usually improves without residual dementia. (30)

Benzodiazepines, ECT are the usual treatments

Experience dictates that the general principles of treatment noted in Table 7 (12,15,23,31) apply to all patients with catatonia. Since the first reported improvement of catatonia with amobarbital in 1930, (6) there have been no controlled studies of specific treatments of catatonia. (13) Meaningful treatment trials are either naturalistic, or have been performed only for NMS and malignant catatonia. (5) However, multiple case reports and case series suggest that treatments with agents that have anticonvulsant properties (benzodiazepines, barbiturates) and ECT are effective. (5)

Benzodiazepines and related compounds. Case series have suggested a 60% to 80% remission rate of catatonia with benzodiazepines, the most commonly utilized of which has been lorazepam. (7,13,32) Treatment begins with a lorazepam challenge test of 1 to 2 mg in adults and 0.5 to 1 mg in children and geriatric patients, (9,15) administered orally (including via nasogastric tube), IM, or IV. Following a response ([greater than or equal to] 50% improvement), the dose is increased to 2 mg 3 times per day. The dose is further increased to 6 to 16 mg/d, and sometimes up to 30 mg/d. (9,11) Oral is less effective than sublingual or IM administration. (11) Diazepam can be helpful at doses 5 times the lorazepam dose. (9,17) A Zolpidem challenge test of 10 mg orally or via nasogastric tube has also been utilized. (15) Response is brief and is usually followed by lorazepam, although Zolpidem up to 40 mg/d has been used for ongoing treatment. (9)

One alternative benzodiazepine protocol utilizes an initial IV dose of 2 mg lorazepam, repeated 3 to 5 times per day the dose is increased to 10 to 12 mg/d if the first doses are partially effective. (16) A lorazepam/ diazepam approach involves a combination of IM lorazepam and IV diazepam. (11) The protocol begins with 2 mg of IM lorazepam. If there is no effect within 2 hours, a second 2 mg dose is administered, followed by an IV infusion of 10 mg diazepam in 500 ml of normal saline at 1.25 mg/hour until catatonia remits.

An Indian study of 107 patients (mean age 26) receiving relatively low doses of lorazepam (3 to 6 mg/d for at least 3 days) found that factors suggesting a robust response include a shorter duration of catatonia and waxy flexibility, while passivity, mutism, and auditory hallucinations describing the patient in the third person were associated with a poorer acute response. (31) Catatonia with marked retardation and mutism complicating schizophrenia, especially with chronic negative symptoms, may be associated with a lower response rate to benzodiazepines. (20,33) Maintenance lorazepam has been effective in reducing relapse and recurrence. (11) There are no controlled studies of maintenance treatment with benzodiazepines, but clinical reports suggest that doses in the range of 4 to 10 mg/d are effective. (32)

ECT was first used for catatonia in 1934, when Laszlo Meduna used chemically induced seizures in catatonic patients who had been on tube feeding for months and no longer needed it after treatment. (6,7) As was true for other disorders, this approach was replaced by ECT. (7) In various case series, the effectiveness of ECT in catatonia has been 53% to 100%. (7,13,15) Right unilateral ECT has been reported to be effective with 1 treatment. (21) However, the best-established approach is with bitemporal ECT with a suprathreshold stimulus, (9) usually with an acute course of 6 to 20 treatments. (20) ECT has been reported to be equally safe and effective in adolescents and adults. (34) Continued ECT is usually necessary until the patient has returned to baseline. (9)

ECT usually is recommended within 24 hours for treatment-resistant malignant catatonia or refusal to eat or drink, and within 2 to 3 days if medications are not sufficiently effective in other forms of catatonia. (12,15,20) If ECT is initiated after a benzodiazepine trial, the benzodiazepine antagonist flumazenil is administered first to reverse the anticonvulsant effect. (9) Some experts recommend using a muscle relaxant other than succinylcholine in the presence of evidence of muscle damage. (7)

Alternatives to benzodiazepines and ECT. Based on case reports, the treatments described in Table 8 (13,15,17,20,25) (page 24) have been used for patients with catatonia who do not tolerate or respond to standard treatments. The largest number of case reports have been with NMDA antagonists, while the presumed involvement of reduced dopamine signaling suggests that dopaminergic medications should be helpful. Dantrolene, which blocks release of calcium from intracellular stores and has been used to treat malignant hyperthermia, is sometimes used for NMS, often with disappointing results.

Whereas first-generation antipsychotics definitely increase the risk of catatonia and second-generation antipsychotics (SGAs) probably do so, SGAs are sometimes necessary to treat persistent psychosis in patients with schizophrenia who develop catatonia. Of these medications, clozapine may be most desirable because of low potency for dopamine receptor blockade and modulation of glutamatergic signaling. Partial dopamine agonism by aripiprazole, and the potential for increased subcortical prefrontal dopamine release resulting from serotonin 5HT2A antagonism and 5HT1A agonism by other SGAs, could also be helpful or at least not harmful in catatonia. Lorazepam is usually administered along with these medications to ameliorate treatment-emergent exacerbation of catatonia.

There are no controlled studies of any of these treatments. Based on case reports, most experts would recommend initiating treatment of catatonia with lorazepam, followed by ECT if necessary or in the presence of life-threatening catatonia. If ECT is not available, ineffective, or not tolerated, the first alternatives to be considered would be an NMDA antagonist or an anticonvulsant. (20)

Course varies by patient, underlying cause

The response to benzodiazepines or ECT can vary from episode to episode (11) and is similar in adults and younger patients. (22) Many patients recover completely after a single episode, while relapse after remission occurs repeatedly in periodic catatonia, which involves chronic alternating stupor and excitement waxing and waning over years. (11) Relapses may occur frequently, or every few years. (11) Some cases of catatonia initially have an episodic course and become chronic and deteriorating, possibly paralleling the original descriptions of the natural history of untreated catatonia, while malignant catatonia can be complicated by medical morbidity or death. (4) The long-term prognosis generally depends on the underlying cause of catatonia. (5)

In general, presentations of catatonia are not specific to any psychiatric or medical etiology

Periodic catatonia refers to recurrent, brief hypokinetic or hyperkinetic episodes lasting 4 to 10 days

Catatonia is more common in mood disorders, particularly mixed bipolar disorder, than in schizophrenia

Up to one-quarter of cases of catatonia are secondary to medical (mostly neurologic) factors or substances

Some psychiatric and medical disorders can mimic and/or cause catatonia, which can make the differential diagnosis complex

Treatment with agents that have anticonvulsant properties (benzodiazepines, barbiturates) and ECT are effective

In case series, the effectiveness of electroconvulsive therapy for catatonia has been 53% to 100%

Much more common than many clinicians realize, catatonia can be overlooked because symptoms can mimic or overlap with features of an underlying medical or neurologic disorder. Suspect catatonia when one of these illnesses has an unexpected course or an inadequate treatment response. Be alert to characteristic changes in behavior and speech. A benzodiazepine challenge can be used to diagnose and begin treatment of catatonia. Consider electroconvulsive therapy sooner rather than later, especially for severely ill patients.

Most experts would recommend initiating treatment of catatonia with lorazepam, followed by ECT if necessary

Many patients with catatonia recover completely after a single episode

Dr. Steven L. Dubovsky receives grant or research support from Allergan, Janssen, Neurim, Neurocrine, and Tower Foundation. Dr. Amelia N. Dubovsky reports no financial relationships with any company whose products are mentioned in this article, or with manufacturers of competing products.

Steven L. Dubovsky, MD Professor and Chair Department of Psychiatry State University of New York at Buffalo Buffalo, New York Adjoint Professor of Psychiatry and Medicine University of Colorado Aurora, Colorado

Amelia N. Dubovsky, MD Assistant Professor Department of Psychiatry University of Washington Seattle, Washington

(1.) Kahlbaum KL. Catatonia. Baltimore, MD: John Hopkins University Press 1973.

(2.) Kahlbaum KL. Die Katatonie oder das Spannungsirresein. Berlin: Hirschwald 1874.

(3.) Tang VM, Duffin J. Catatonia in the history of psychiatry: construction and deconstruction of a disease concept. Perspect Biol Med. 201457(4):524-537.

(4.) Carroll BT. Kahlbaum's catatonia revisited. Psychiatry Clin Neurosci. 200155(5):431-436.

(5.) Taylor MA, Fink M. Catatonia in psychiatric classification: a home of its own. Am J Psychiatry. 2003160(7):1233-1241.

(6.) Fink M, Fricchione GL, Rummans T, et al. Catatonia is a systemic medical syndrome. Acta Psychiatr Scand. 2016133(3):250-251.

(7.) Medda P, Toni C, Luchini F, et al. Catatonia in 26 patients with bipolar disorder: clinical features and response to electroconvulsive therapy. Bipolar Disord. 201517(8): 892-901.

(8.) Mazzone L, Postorino V, Valeri G, et al. Catatonia in patients with autism: prevalence and management. CNS Drugs. 201428(3):205-215.

(9.) Fink M, Kellner CH, McCall WV. Optimizing ECT technique in treating catatonia. J ECT. 201632(3):149-150.

(10.) Kocha H, Moriguchi S, Mimura M. Revisiting the concept of late catatonia. Compr Psychiatry. 201455(7):1485-1490.

(11.) Lin CC, Hung YL, Tsai MC, et al. Relapses and recurrences of catatonia: 30-case analysis and literature review. Compr Psychiatry. 201666:157-165.

(12.) Saddawi-Konefka D, Berg SM, Nejad SH, et al. Catatonia in the ICU: An important and underdiagnosed cause of altered mental status. A case series and review of the literature. Crit Care Med. 201342(3):e234-e241.

(13.) Wijemanne S, Jankovic J. Movement disorders in catatonia, J Neurol Neurosurg Psychiatry. 201586(8):825-832.

(14.) Grover S, Chakrabarti S, Ghormode D, et al. Catatonia in inpatients with psychiatric disorders: a comparison of schizophrenia and mood disorders. Psychiatry Res. 2015229(3):919-925.

(15.) Oldham MA, Lee HB. Catatonia vis-a-vis delirium: the significance of recognizing catatonia in altered mental status. Gen Hosp Psychiatry. 201537(6):554-559.

(16.) Tuerlings JH, van Waarde JA, Verwey B. A retrospective study of 34 catatonic patients: analysis of clinical ' care and treatment. Gen Hosp Psychiatry. 201032(6): 631-635.

(17.) Ohi K, Kuwata A, Shimada T, et al. Response to benzodiazepines and the clinical course in malignant catatonia associated with schizophrenia: a case report. Medicine (Baltimore). 2017,-96(16):e6566. doi: 10.1097/ MD.0000000000006566.

(18.) Komatsu T, Nomura T, Takami H, et al. Catatonic symptoms appearing before autonomic symptoms help distinguish neuroleptic malignant syndrome from malignant catatonia. Intern Med. 201655(19):2893-2897.

(19.) Lang FU, Lang S, Becker T, et al. Neuroleptic malignant syndrome or catatonia? Trying to solve the catatonic dilemma. Psychopharmacology (Berl). 2015232(1):1-5.

(20.) Beach SR, Gomez-Bernal F, Huffman JC, et al. Alternative treatment strategies for catatonia: a systematic review. Gen Hosp Psychiatry 201748:1-19.

(21.) Kugler JL, Hauptman A], Collier SJ, et al. Treatment of catatonia with ultrabrief right unilateral electroconvulsive therapy: a case series, j ECT. 201531(3): 192-196.

(22.) Raffin M, Zugaj-Bensaou L, Bodeau N, et al. Treatment use in a prospective naturalistic cohort of children and adolescents with catatonia. Eur Child Adolesc Psychiatry. 201524(4):441-449.

(23.) Dejong H, Bunton P, Hare DJ. A systematic review of interventions used to treat catatonic symptoms in people with autistic spectrum disorders. J Autism Dev Disord. 201444(9):2127-2136.

(24.) Wachtel L, Commins E, Park MH, et al. Neuroleptic malignant syndrome and delirious mania as malignant catatonia in autism: prompt relief with electroconvulsive therapy. Acta Psychiatr Scand. 2015132(4):319-320.

(25.) Fink M, Taylor MA. Catatonia: subtype or syndrome in DSM? Am J Psychiatry. 2006163(11):1875-1876.

(26.) Khan M, Pace L, Truong A, et al. Catatonia secondary to synthetic cannabinoid use in two patients with no previous psychosis. Am J Addictions. 201625(1):25-27.

(27.) Komatsu T, Nomura T, Takami H, et al. Catatonic symptoms appearing before autonomic symptoms help distinguish neuroleptic malignant syndrome from malignant catatonia. Intern Med. 201655(19):2893-2897.

(28.) Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association 2013.

(29.) Wilson JE, Niu K, Nicolson SE, et al. The diagnostic criteria and structure of catatonia. Schizophr Res. 2015164(1-3): 256-262.

(30.) Ducharme S, Dickerson BC, Larvie M, et al. Differentiating frontotemporal dementia from catatonia: a complex neuropsychiatric challenge. J Neuropsychiatry Clin Neurosci. 201527(2):e174-e176.

(31.) Narayanaswamy JC, Tibrewal P, Zutshi A, et al. Clinical predictors of response to treatment in catatonia. Gen Hosp Psychiatry. 201234(3):312-316.

(32.) Thamizh JS, Harshini M, Selvakumar N, et al. Maintenance lorazepam for treatment of recurrent catatonic states: a case series and implications. Asian J Psychiatr. 201622:147-149.

(33.) Ungvari GS, Chiu HF, Chow LY, et al. Lorazepam for chronic catatonia: a randomized, double-blind, placebocontrolled cross-over study Psychopharmacology (Berl). 1999142(4):393-398.

(34.) Hamarique I, Baeza I, de la Serna E, et al. Long-term effectiveness of electroconvulsive therapy in adolescents with schizophrenia spectrum disorders. Eur Child Adolesc Psychiatry. 201524(5):517-524.

Can anticholinergics like benztropine be used to treat Catatonia? - Psychology

Catatonia is a commonly encountered syndrome, affecting 10–20% of various psychiatric populations and carrying significant medical co-morbidities. However, there are few established alternative treatment strategies when benzodiazepines are ineffective and electroconvulsive therapy is unavailable.


The authors systematically review evidence for alternative treatment strategies for catatonia using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines.


The authors conducted a search of PubMed database from 1983 to August 2016 to identify articles. Eligible reports presented cases involving treatment of catatonia using modalities other than benzodiazepines or electroconvulsive therapy.


The authors identified 72 articles, comprising 98 individual cases. N-methyl- d -aspartate-receptor antagonists, anti-epileptic drugs, and atypical antipsychotic agents appeared to have the largest number of reports supporting their effectiveness and safety in treating catatonia patients.


Based on the case report literature, the authors propose an updated algorithm for catatonia treatment in cases where benzodiazepines fail and electroconvulsive therapy is not available.


  1. Berne

    This magnificent thought, by the way, falls

  2. Caladh

    As that interestingly sounds

  3. Kekinos

    You are wrong. Email me at PM, we will discuss.

  4. Joosef

    the Intelligible message

Write a message