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Similarities and Differences in Agitation Associated with Schizophrenia and Bipolar Disorder

Faculty Perspectives: Similarities and Differences in Agitation Associated with Schizophrenia and Bipolar Disorder

Agitation refers to a spectrum of abnormal behaviors often seen in patients with various psychiatric illnesses, including those with schizophrenia or bipolar disorder.1 It is a mental and physical state that is characterized by motor restlessness, mental tension, and excitement, and is often marked by poorly organized, aimless psychomotor activity.1 Agitation may escalate into physical aggression, resulting in emergency department visits, admissions to psychiatric wards, and continued hospitalization.2-4 Therefore, it is essential that agitated patients be accurately diagnosed and effectively managed to decrease the risk that they will cause harm to themselves or others.

The differential diagnosis of agitation that accompanies schizophrenia or bipolar disorder can only be determined after a careful evaluation of the patient and consideration of all factors that may be contributing to an agitated state.2 For example, involuntary motor activity may be a side effect of prescribed therapies for a patient’s disorder, or it may be a symptom of an underlying or comorbid somatic illness. In addition, since approximately 50% of patients with schizophrenia have a comorbid substance abuse disorder,5-7 it is important to consider whether agitation is accompanying withdrawal from abused substances. Akathisia, which is defined as a sensation of inner restlessness, may be caused by the use of antipsychotic drugs and antidepressants.2,8 It is imperative for providers to differentiate between akathisia and agitation because improper dosing may lead to the worsening of akathisia-related symptoms.2

Healthcare workers can use a variety of assessment scales (eg, Positive and Negative Syndrome Scale, Excited Component [PANSS-EC]) to assess the severity of agitation in the context of psychotic illnesses.9 These assessment tools measure agitation on a scale that ranges from anxiety to aggression. The scale reveals the 3 major components of most instances of agitation: (1) strong emotion, (2) excessive motor or vocal activity, and (3) inappropriate motor or vocal activity.9

Agitation Associated with Bipolar Disorder and Schizophrenia
Bipolar Disorder

Bipolar disorder is characterized by extreme shifts in mood and energy levels10; patients may also experience shifts in thinking and sleep patterns. In addition, behavioral changes are frequently observed, differentiating the manic phase from the depressive phase.10 However, even with characteristic behavioral and mood shifts, bipolar disorder may be difficult to diagnose.11 In one survey, patients waited at least 10 years before obtaining an accurate diagnosis, and more than half the patients diagnosed with bipolar disorder believed that their physicians had a fundamental lack of understanding of the disorder, which contributed to the delay.12 Another survey showed that 69% of patients were misdiagnosed initially, and that one-third remained misdiagnosed for 10 or more years.11 This may be due partly to the fact that, because patients often visit physicians when they are depressed and are, therefore, treated for simple clinical depression, their bipolar depression is misdiagnosed as a major depressive disorder.11 Individuals also may not give accurate accounts of manic or hypomanic episodes to their physicians.

In bipolar disorder, agitation often manifests during manic episodes as excess activity, and during depressive episodes, as irritability and fluctuating energy levels.6 Detailed studies of patients with bipolar disorder have revealed that agitation that escalates into aggression is a common presentation of a manic episode.13 In the manic state of bipolar disorder, agitated patients may have racing thoughts, pressured speech, and increased motor activity. Some patients may also exhibit a “paranoia-aggression-irritability cluster.”4 Agitation may also occur during the depressive phase of bipolar disorder.4 Furthermore, psychotic symptoms in bipolar I disorder (ie, intrusive/commanding hallucinations, paranoid delusions) may cause agitation and be associated with unpredictable and aggressive behavior.1,2

Schizophrenia

Schizophrenia is a chronic recurring psychotic disorder that is characterized by impaired thinking, behavior, and emotions. In the majority of patients, schizophrenia negatively affects normal social and occupational functioning.14 Patients typically present with distinct psychopathologic symptoms; these are classified as positive symptoms, negative symptoms, mood symptoms, anxiety symptoms, and cognitive impairment.15,16

In schizophrenia, agitation may be a reflection of delusions (eg, jealousy of a partner, persecutory delusion) and/or command hallucinations to harm others; the danger here is that agitation may lead to violence.7,13 Many factors contribute to aggressive behavior in patients with schizophrenia, and the root cause may not always be apparent.17 Substance abuse, cognitive impairment, prenatal exposure to toxins, genotype, childhood abuse, and other circumstances may contribute to aggressive behavior; knowing the full history of the patient should guide clinicians to choose the most appropriate therapies.17

Nonpharmacologic Interventions for Patients with Agitation

In general, agitation associated with either bipolar disorder or schizophrenia is best managed by de-escalation techniques, including in emergency department situations.18 Because patients with these diseases are likely to present with psychomotor agitation, verbal de-escalation skills should be part of the practitioner’s repertoire in any treatment setting. These skills include maintaining a safe personal space, adopting a calm demeanor and facial expression, speaking calmly at a low volume, listening well, offering choices regarding treatment, and, finally, debriefing the patient and staff.19 Consensus guidelines indicate that calming rather than sedating the patient should be the goal of immediate treatment for acute agitation.9,20 Restraint and seclusion should only be used as last resorts in emergency situations, when there is risk for imminent harm.9,21 The environment should be assessed, and all objects that could be used as weapons should be removed discreetly. As a point of safety, medical personnel should always face the patient, engaging him or her in soft yet authoritative tones.1

Pharmacologic Interventions for Patients with Agitation

One of the goals of administering medication to agitated patients is to calm them so that practitioners can better assess their symptoms. In general, barbiturates, benzodiazepines, and typical antipsychotics have long been the mainstays of treatment for agitation associated with bipolar disorder or schizophrenia, followed more recently by atypical antipsychotics.9 Route of administration is a key consideration in selecting appropriate drugs, because, in general, orally administered drugs take substantially longer to take effect than intramuscularly administered drugs.

Pharmacologic treatment of agitation may include the use of a sublingual antipsychotic, which has efficacy comparable with those of injectable antipsychotics.22 Nevertheless, only 55% of patients who are severely agitated are successfully managed with regular oral drugs alone.9

Intramuscular (IM) anxiolytic drugs (eg, benzodiazepines) are often used to treat patients with schizophrenia or bipolar disorder who have severe agitation. Although these agents have a rapid onset of action, they also have some undesirable adverse effects, including respiratory depression and rare paradoxical behavioral effects.2 Another consideration is that the use of hypodermic syringes poses hazards to medical personnel, especially when dealing with agitated patients.23

A therapeutic advancement in the treatment of agitated patients with bipolar disorder or schizophrenia is the recent development and approval of a first-generation antipsychotic drug that uses an inhalation-activated aerosol as its delivery modality.2,23 This drug is an antagonist at the dopamine D2 receptor, with clinically relevant serotonin 5-HT2A receptor antagonism. The delivery method does not require hand and breath coordination, as it is activated by the patient’s inhalation via a sensor in the delivery device, which in turn initiates the vaporization of the drug, which enters the respiratory tract in less than 1 second without the need for forceful inhalation.2 The emitted dose is approximately 90% of the drug in the device; there are no excipients,2,24 and only a small amount of the drug is deposited in the oropharyngeal tract.25 Importantly, before administering the inhaled antipsychotic, patients must be screened for a history of pulmonary disease, because the drug may cause bronchospasm.2

Several clinical trials have demonstrated the safety and efficacy of this orally inhaled drug.26-28 No excess sedation was noted, and the most common adverse event was dysgeusia; other side effects included sedation and somnolence, throat irritation, and extrapyramidal symptoms.2,23 In one study of patients with agitation associated with bipolar disorder, reduced agitation was reported within 10 minutes after administering this inhaled antipsychotic (5 mg or 10 mg), as assessed by the PANSS-EC tool.28 Another clinical trial in patients with agitation associated with schizophrenia showed similar results, where this inhaled drug (5 mg or 10 mg) significantly reduced agitation compared with placebo 10 minutes after administration.27

Conclusions

In the setting of agitation associated with bipolar disorder and schizophrenia, nonpharmacologic considerations should focus on maintaining the safety of patients and others. Whenever possible, de-escalation strategies should be implemented before medication is administered. Medications currently approved by the US Food and Drug Administration for the treatment of patients with agitation include short-acting IM formulations of atypical antipsychotics, as well as a newer inhaled antipsychotic. In contrast to agitation associated with schizophrenia or bipolar mania, no agents have yet been approved by regulatory agencies for the treatment of persistent aggressive behavior. Clearly, longer-term management of persistent aggressive behavior by reducing the frequency and intensity of future episodes of agitation is complex and should be the focus of ongoing studies.29

References

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Last modified: August 30, 2021