Impact of Abrupt Interruption of Home Psychotropic Medications at ICU Admission

Abstract

Background: Abrupt discontinuation of home psychotropic medications is common among critically ill patients but may precipitate clinically significant withdrawal. Objective: To determine the percent of patients with interruptions in home psychotropic medications upon intensive care unit (ICU) admission and to identify outcomes associated with these interruptions. Methods: This was an institutional review board-approved, single-center, retrospective study of critically ill patients with a history of mental illness taking an antipsychotic or antidepressant medication. The primary outcome was the percent of patients with interruption in at least one home psychotropic medication for ≥24 hours upon ICU admission. Secondary outcomes included time to psychotropic re-initiation, percent of home psychotropic medications restarted in the ICU, ICU length of stay (LOS), delirium, withdrawal-related complications, need for acute antipsychotics or benzodiazepines, and reasons for psychotropic interruption. Results: Among 183 patients, 93 (50.8%) had interruptions in home psychotropic therapy for ≥24 hours upon ICU admission. Mean time to reinitiation of at least one psychotropic agent was 1.4 days, and 16.4% of patients did not have any home psychotropics restarted. Patients with psychotropic interruption had a longer ICU LOS (P = 0.01) and greater incidence of ICU delirium (P < 0.01). Withdrawal-related complications were similar between groups. Acute antipsychotic use was greater in patients with psychotropic interruption (P < 0.01). Acute benzodiazepine use was not different between groups (P = 0.87). Most patients did not have a documented reason for therapy interruption. Conclusion and Relevance: Unless contraindicated, clinicians should attempt to restart home psychotropic medications as soon as possible in critically ill patients.

Introduction

Mental health disorders are highly prevalent in the US population, with an estimated 52.9 million people meeting Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for at least one disorder in 2020. ¹ These disorders include, but are not limited to, conditions such as major depressive disorder, anxiety disorder, schizophrenia, psychosis, and bipolar disorder, which may significantly alter a person’s thinking, behavior, or mood. ² In conjunction with cognitive behavioral therapy, medications are frequently used to treat mental health disorders. Two of the most common classes of medications used in practice include antidepressants and antipsychotics.^1,2

Critically ill patients are a unique population where comorbid psychiatric illnesses may be aggravated in the acute setting. This may be due to the multitude of changes taking place in the patient’s environment and physical condition. For example, many patients experience feelings of demoralization, depression, anxiety, and fear due to loss of bodily autonomy and threats of disability or death. ³ Critical illness itself may also be associated with psychiatric manifestations.^3,4 In addition, many physicians reflexively discontinue chronic medications, including psychiatric therapies, upon hospital admission in fear of potential adverse effects and drug interactions. ⁵ However, only about 10% to 15% of hospitalized patients actually require discontinuation of their home psychotropics. ⁴ In intensive care unit (ICU) patients, these medications may be held for reasons such as an upcoming surgical procedure, hemodynamic instability, or incompatible dosage form. Psychotropic medications such as selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), and antipsychotics often require tapering to prevent clinically significant withdrawal syndromes, which may become apparent within the first few days of discontinuation.^6,7 Serious withdrawal-related complications may include psychiatric decompensation with a rapid onset of psychosis, increased agitation, delirium, insomnia, gastrointestinal (GI) upset, headache, confusion, and other mood changes.^5,7,8 These complications may also be masked by concurrent medications such as opioid analgesics, benzodiazepines, and other sedating agents. ⁸ Furthermore, withdrawal from antidepressant medications can be mistaken for hyperactive delirium, which is common (approximately 4% of all patients) but underdiagnosed in ICU patients. ⁹

There is a paucity of data in the literature, some of which is conflicting, on the effects of psychotropic medication interruption in critically ill patients. La et al ⁶ found that early restart of home neuropsychiatric medications within 5 days of ICU admission led to lighter sedation levels, less delirium, and fewer ventilator days. Another study demonstrated similar results with a reduction in delirium, irritability, and agitation among patients with early reinitiation of antidepressant therapy. ⁸ However, a recent study by Cucci et al ¹⁰ found no significant difference in agitation or delirium between cohorts. Furthermore, new-start antipsychotic use for treatment of delirium and ICU length of stay (LOS) have not been found to differ significantly.^6,11

Failure to reinitiate home psychotropic medications is hypothesized to be under-documented in the ICU and potentially causes serious withdrawal sequelae. As a result, this may lead to increased use of as needed (“PRN”) medications, such as benzodiazepines and antipsychotics. The purpose of this study was to quantify the number of patients with interruptions in home psychotropic therapy upon ICU admission and to identify any negative outcomes associated with these interruptions.

Methods

This was an institutional review board-approved, single-center, retrospective study of patients admitted to an ICU with a history of mental health disorder taking a psychotropic medication prior to admission. An analytics report identified all eligible patients admitted to an ICU between January 2019 and June 2021. Patients were included if they were 18 years of age or older, were admitted to any ICU for at least 24 hours, had a documented history of mental health disorder, and were prescribed a psychotropic medication prior to admission. History of mental health disorder was determined by documentation of International Classification of Diseases, Tenth Revision (ICD-10) codes for the following disorders: schizophrenia, schizotypal disorder, schizoaffective disorders, other psychotic disorders not due to a substance or known physiological condition, unspecified psychosis not due to a substance or known physiological condition, bipolar disorder, depressive episode, major depressive disorder, persistent mood disorder, unspecified mood disorder, and anxiety disorder. Psychotropic medications included first- and second-generation antipsychotics or antidepressants (SSRI, SNRI, tricyclic antidepressant [TCA], monoamine oxidase inhibitor [MAOI], and atypical antidepressant). Patients were excluded if they were taking a long-acting injectable antipsychotic medication prior to admission, had overdosed on their home psychotropic medication, or if they had a diagnosis of COVID-19, substance use disorder, traumatic brain injury, or seizure disorder.

The primary outcome was the percent of patients with interruption in at least one home psychotropic medication for 24 hours or longer upon ICU admission. Secondary outcomes included percent of all home psychotropic medications restarted in the ICU, time to home psychotropic reinitiation, ICU LOS, withdrawal-related complications, need for acute antipsychotics or benzodiazepines, and reasons for psychotropic interruption. The following data were extracted from the electronic medical record: patient demographics, ICU location, number and type of mental health disorders, home medications, nursing assessments, and inpatient medications. Time to psychotropic reinitiation was measured as discrete days from ICU admission (ie, within X days of admission). Withdrawal-related complications included delirium, insomnia, and GI upset. Incidence of delirium was measured by documentation of at least one positive score on the Confusion Assessment Method for the ICU (CAM-ICU). Incidence of other withdrawal-related complications was determined by reviewing provider progress notes for symptom documentation and reviewing the medication administration record (MAR) to assess whether ancillary medications were administered for insomnia or GI upset. Only new-start sleep medications and antiemetics were considered when evaluating patients for these specific withdrawal symptoms. Reasons for psychotropic interruption were determined through review of provider and nursing progress notes or, in the case of an inability to administer the dosage form, through documentation of NPO (nothing by mouth) status in the MAR.

The rationale for selecting a time interval of at least 24 hours for psychotropic interruption was based upon the earliest anticipated onset time for withdrawal and discontinuation symptoms to appear. Withdrawal syndromes typically develop within 3 days of cessation of a chronic psychiatric drug but can also occur as early as 24 hours after the first missed dose.^7,12 Peak onset of withdrawal tends to occur more rapidly with drugs that have shorter half-lives. In addition, due to the study period taking place during the peak of the COVID-19 pandemic, we excluded patients with an active diagnosis of COVID-19. We anticipated that a significant majority of our population would have been comprised of patients hospitalized for COVID-19, making our results less generalizable to those admitted for other disease states. COVID-19 admission also had the potential to impact secondary outcomes due to prolonged ICU LOS and potential psychiatric sequelae of the disease course itself.

Data analysis was conducted using descriptive statistics, including counts and percentages for categorical variables, and means and standard deviations for continuous data. Fischer exact test was used for categorical data and a two-tailed, independent t-test was used for continuous data. Statistical significance was defined as P ≤ 0.05.

Results

A total of 183 critically ill patients were included in the study (Table 1). The majority of patients were white and female with a mean age of 68 ± 15 years. Among 47 patients admitted to a medical ICU, 35 (74.5%) had interruptions in home psychotropic therapy. Depression and anxiety were the 2 most common mental health disorders, and many patients (26.8%) had more than one mental health disorder. Among all patients, SSRIs were the most common type of home psychotropic agent. Very few patients were taking a first-generation antipsychotic or TCA, and no patients were taking an MAOI. Patients with therapy interruption were more likely to be taking multiple psychoactive medications at home than those with no interruption (39.8% vs 20.0%, P < 0.01). The mean number of home psychotropic agents was 1.2 ± 0.5 in patients without interruptions in therapy and 1.6 ± 0.8 in patients who had interruptions in therapy.

Table 1.

Baseline Demographics.

Demographic	No interruption (n = 90)	Interruption (n = 93)
Age, y a	68 ± 14	67 ± 6
Male b	33 (36.7)	31 (33.3)
Race b
White	53 (58.9)	55 (59.1)
Hispanic	17 (18.8)	18 (19.4)
Black	14 (15.6)	13 (14.0)
Asian	0 (0.0)	1 (1.1)
Other	6 (6.7)	6 (6.4)
ICU type b
Medical	12 (13.3)	35 (37.6)
Surgical	18 (20.0)	6 (6.5)
Cardiac	22 (24.5)	15 (16.1)
Mixed	38 (42.2)	37 (39.8)
Mental illness diagnosis b
Depression	53 (58.9)	63 (67.7)
Anxiety	45 (50.0)	39 (41.9)
Schizophrenia	5 (5.6)	10 (10.8)
Bipolar disorder	2 (2.2)	7 (7.5)
Schizoaffective disorder	2 (2.2)	2 (2.1)
Non-schizophrenia psychosis	2 (2.2)	1 (1.1)
Multiple	21 (23.3)	28 (30.1)
Type of home psychotropic agent b
SSRI	66 (73.3)	46 (49.5)
Atypical antidepressant	16 (17.8)	35 (37.6)
Second-generation antipsychotic	16 (17.8)	34 (36.6)
SNRI	12 (13.3)	15 (16.1)
TCA	1 (1.1)	6 (6.5)
First-generation antipsychotic	1 (1.1)	3 (3.2)
MAOI	0 (0.0)	0 (0.0)
Multiple	18 (20.0)	37 (39.8)
Number of home psychotropic agents a	1.2 ± 0.5	1.6 ± 0.8

Abbreviations: ICU, intensive care unit; MAOI, monoamine oxidase inhibitor; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant.

^aMean ± SD.

^bNo. (%).

Following ICU admission, 93 of 183 patients (50.8%) had interruption in at least one home psychotropic medication for 24 hours or longer. Incidence of and time to psychotropic mediation reinitiation is summarized in Table 2. Among patients with therapy interruption, 42 (45.2%) had all home psychiatric medications restarted at any point during the ICU stay, 17 (18.3%) had at least half of their medications restarted, 3 (3.2%) had less than half of their medications restarted, and 31 (33.3%) did not have any medications restarted. The mean time to re-initiation of at least one psychotropic agent was within 2.6 ± 1.2 days of ICU admission.

Table 2.

Psychotropic Medication Reinitiation (n = 93).

All agents restarted in the ICU a	42 (45.2)
≥50% of agents restarted in the ICU a	17 (18.3)
<50% of agents restarted in the ICU a	3 (3.2)
None restarted a	31 (33.3)
Time to reinitiation, d b	2.6 ± 1.2

Abbreviation: ICU, intensive care unit.

^aNo. (%).

^bMean ± SD.

Other secondary outcomes, including ICU LOS, withdrawal-related complications, and need for acute rescue medications, are described in Table 3. Patients with abrupt interruption in psychotropic therapy had a significantly longer ICU LOS compared with patients with no interruptions in therapy (4.0 vs 2.9 days; P = 0.01). The incidence of delirium, as measured by documentation of at least one positive CAM-ICU, was significantly greater in patients with psychotropic interruption (20.4% vs 3.3%; P < 0.01). Patients with therapy interruption also had a trend toward a longer duration of ICU delirium, although the difference was not statistically significant (mean, 2.7 vs 1.3 days; P = 0.27). There was no difference between groups in the incidence of other withdrawal-related complications, including insomnia (11.8% vs 4.4%; P = 0.10) and GI upset (21.5% vs 18.9%; P = 0.71). However, patients with therapy interruption had a trend toward increased rates of insomnia. The percent of patients with PRN antipsychotic use was greater in the group with psychotropic interruption (15.1% vs 3.3%; P < 0.01). There was no difference between groups in PRN benzodiazepine use (25.8% vs 24.4%; P = 0.87). In patients requiring rescue medications, there was a trend toward greater usage of both types of agents, but the difference was not significant (mean number of antipsychotic doses, 2.6 vs 1.7; P = 0.59 and mean number of benzodiazepine doses, 3.5 vs 2.7; P = 0.51).

Table 3.

Secondary Outcomes (N = 183).

Outcome	No interruption (n = 90)	Interruption (n = 93)	P value
ICU LOS, d a	2.9 ± 2.1	4.0 ± 2.8	0.01
Positive CAM-ICUb,c	3 (3.3)	19 (20.4)	<0.01
Number of days a	1.3 ± 0.5	2.7 ± 2.0	0.27
Insomniab,c	4 (4.4)	11 (11.8)	0.10
Nausea/vomiting/diarrheab,c	17 (18.9)	20 (21.5)	0.71
PRN antipsychotic use b	3 (3.3)	14 (15.1)	<0.01
Number of doses a	1.7 ± 0.5	2.6 ± 2.8	0.59
PRN benzodiazepine use b	22 (24.4)	24 (25.8)	0.87
Number of doses a	2.7 ± 3.5	3.5 ± 4.5	0.51

Abbreviations: CAM-ICU, Confusion Assessment Method for the intensive care unit; ICU, intensive care unit; LOS, length of stay; PRN, as needed.

^aMean ± SD.

^bNo. (%).

^cWithdrawal-related complications.

Reasons for psychotropic medication interruption are listed in Table 4. Most patients with therapy interruption did not have a reason for discontinuation documented in the medical chart (67.7%). The most common documented reasons were inability to administer the drug due to lack of available dosage forms (12.9%), adverse drug reaction or drug interaction (8.6%), and patient refusal (6.5%). Other reasons for psychotropic interruption included surgery, hemodynamic instability, nonformulary drug, and pharmacy delays.

Table 4.

Reasons for Psychotropic Interruption (n = 93) ^a .

No reason documented	63 (67.7)
Inability to administer dosage form	12 (12.9)
Adverse drug reaction or drug interaction	8 (8.6)
Patient refusal	6 (6.5)
Other	4 (4.3)

^aPresented as No. (%).

Discussion

In this retrospective study of 183 critically ill patients, half of our patients had abrupt interruptions in home psychotropic therapy for 24 hours or longer following ICU admission. Medication interruption was associated with a significantly longer ICU LOS, greater incidence of ICU delirium, and more PRN antipsychotic use. In addition, most patients did not have a documented reason in the medical chart for withholding psychiatric therapy.

Patients admitted to a medical ICU had the highest rate of psychotropic interruption among all ICU types, which may be due to differences in the patient population admitted to a medical ICU relative to other ICUs. Medical ICU patients are often admitted with numerous acute medical issues and have an extensive medication list for treatment of these conditions. In contrast, patients in the surgical and cardiac ICUs are not always admitted for acute illness. For example, many of the patients included in our study that were not in the medical ICU were admitted for postoperative monitoring, and therefore may not have been as acutely ill. With a longer and more complicated problem list, there is a greater chance of overlooking a component of patient care such as home medications. There is also a greater probability of drug-drug or drug-disease interactions that could preclude medication reinitiation.

A significant finding of our study is that patients with disruptions in home psychotropic therapy had their ICU LOS prolonged by approximately 1 day. The consequences of longer ICU stays have been well-established and include both short-term and long-term sequelae. Short-term sequelae include a greater risk of hospital-acquired infections, complications such as venous thromboembolism or stress ulcers, mechanical ventilation, and mortality.^13,14 Long-term sequelae include muscle wasting, impaired physical function, cognitive decline, and reduced health-related quality of life.^15,16 Psychological morbidity is highly prevalent as well and may include depression, anxiety, and posttraumatic stress disorder (PTSD).^16,17 This impact may be further augmented in the patient with underlying psychiatric illness and can lead to acute exacerbations of depression, anxiety, or psychosis. Furthermore, prolonged ICU stays are of economic consequence as they increase health care costs and consume a significant share of hospital resources. ¹³ Hence, the potential to reduce ICU LOS by even 1 day is advantageous for both the patient and the health system.

Intensive care unit delirium and acute antipsychotic use were significantly greater in patients with psychotropic interruption, suggesting that patients may have become delirious, agitated, and/or entered acute psychosis due to not restarting their home therapies. It is possible that these effects may have contributed to the longer ICU LOS that this cohort experienced. Although not all withdrawal-related outcomes reached statistical significance, many of these complications trended toward increasing incidence in patients who had psychiatric medications abruptly withdrawn. Reduction in even a few withdrawal symptoms may considerably improve the physical and psychological well-being of a critically ill patient, lending to more favorable long-term outcomes upon hospital discharge. There was no documented reason for therapy interruption in a majority of our patients, suggesting that most patients may not have had a valid indication for discontinuation. Given the numerous complex issues affecting critically ill patients, psychiatric considerations may be an overlooked aspect of care.

Our results share consistencies as well as differences to those of other small observational studies. La et al ⁶ conducted a retrospective cohort study in 106 ventilated ICU patients evaluating the effect of early (≤5 days) versus late (>5 days) restart of home neuropsychiatric medications. Similar to our study, the authors found that patients who were restarted on these medications within 5 days of ICU admission had less ICU delirium than those who were restarted later (17% vs 43%; P = 0.02). Furthermore, Bainum et al ⁸ evaluated the effects of early initiation of home SSRI or SNRI therapy within 24 hours of admission in 106 critically ill patients. They found that these patients had a significant reduction in affective symptoms, defined as a composite of delirium, irritability, or agitation, relative to their counterparts who had abrupt discontinuation of therapy (P = 0.004). However, a study conducted by Cucci et al ¹⁰ and a research abstract published by Staub et al ¹⁸ yielded different results. While the incidence of delirium was greater in patients with late restart of home psychotropic medications in both studies, neither one reached statistical significance (19% vs 35%; P = 0.083 and 33% vs 43%; P = 0.31, respectively). In addition, contrary to the present study, Li et al ¹¹ found no difference in the requirement for new-start antipsychotics (P = 1.0) and no difference in ICU LOS (P = 0.71) among 110 critically ill patients with early (≤24 hours) versus late (>24 hours) restart of home psychotropic medications. La and Bainum’s studies also found no difference in antipsychotic use between cohorts for symptom-targeted management. Of note, all studies were limited by small sample sizes or retrospective design.

Our study had some limitations. First, this was a retrospective study conducted at a single health system with a relatively small sample size. As all data were dependent on chart review, we may not have captured all withdrawal-related complications occurring in our patients due to lack of documentation in provider progress notes. This is an important limitation to consider when evaluating the incidence of insomnia, nausea, vomiting, and diarrhea since this information is not routinely documented. Furthermore, patients may have had other medical causes contributing to their withdrawal-type symptoms outside of psychotropic interruption. Second, there was no way to assess the accuracy of the medication reconciliations documented prior to admission. It is possible that patients may have been noncompliant with their prescribed medication, were taking additional psychotropic medications not captured in the home medication list, or that one or more medications had been discontinued prior to admission. To account for this possibility, we referenced multiple sources for home medications during the data collection process. This included medication reconciliations for current and previous admissions, discharge orders from previous admissions, and external pharmacy prescription fill records, if available. Finally, ICU LOS may have been impacted by other confounding factors within the study population. As mentioned previously, patients with psychotropic interruption were more likely to be admitted to a medical ICU, which may represent a population with a higher severity of illness. It remains unclear whether psychotropic interruption itself or baseline differences between groups led to the prolonged LOS seen in these patients.

Conclusion and Relevance

In this retrospective chart review of 183 critically ill patients, most patients had interruptions in home psychotropic therapy for ≥24 hours following ICU admission. The lack of documented reasoning for therapy interruption suggests that many patients may not have had a valid indication for discontinuation. Clinicians should avoid psychotropic medication interruption in critically ill patients to minimize ICU delirium, acute antipsychotic use, and ICU LOS. Larger, prospective studies are warranted to confirm the results from this study and to further assess the impact of psychiatric withdrawal in this vulnerable patient population.