Patient Safety Tip of the Week
March 20, 2012
Adverse Events Related to Psychotropic Medications
We’ve seen an explosive growth in the prescription of psychotropic medications in the past decade so it should come as no surprise that we are also seeing more frequent adverse events related to them.
Studies on inpatient psychiatry units have revealed overall rates of adverse drug events and medication errors to be similar to those seen on general hospital patients (Rothschild 2007). Of the psychotropic drugs the class of atypical antipsychotic drugs accounted for the most adverse drug events.
A couple articles recently have highlighted some of the
issues related to psychotropic drugs. The first was one regarding the relative
risk of death in older residents of nursing homes prescribed antipsychotic
medications (Huybrechts
2012). It has been known for some time now that the atypical antipsychotic
drugs were associated with an increased risk of cerebrovascular incidents and
death. In 2005 the FDA added black box warnings about the risk for death for
these drugs when used in the elderly with dementia and then added similar
warnings in 2008 for the more traditional antipsychotic drugs. Yet they
continue to be widely prescribed in the nursing home setting. The Huybrechts
paper quantifies the risks of the individual drugs in the nursing home setting.
They used a large Medicare and Medicaid dataset and were able to determine the
relative mortality risks for a variety of the antipsychotic drugs relative to
their reference drug resperidone. They found that haloperidol had over double
the risk of death compared to resperidone and that the effects were strongest
shortly after starting the drug. Quetiapine had a slightly reduced risk
compared to resperidone and most of the other antipsychotics had risks similar
to resperidone. In general, the risks increased as the dosage was increased for
all the drugs except quetiapine. It’s hard to justify use of these drugs in
this population, given their limited efficacy and these significant risks. The
authors caution that, when they must be used (when non-pharmacologic
interventions have failed), they should be used in the lowest doses possible
and the patients should be carefully monitored.
The second article
was an analysis by ISMP Canada of incidents involving psychotropic medications
(ISMP
Canada 2012). They found that of almost 80,000 medication incidents
reported over an 11-year period 7.4% involved psychotropic medications. And of
the latter 2.3% were associated with patient harm. They found incidents spanning
nearly all healthcare settings and several themes were seen in three main
settings: the community, the hospital, and the long-term care settings.
In the community
setting they found 3 main themes: (1) multiple medication theme (2) incorrect
medication theme and (3) incorrect patient theme. They point out that in
patients taking multiple psychotropic medications it is often difficult to sort
out what side effects are due to which medication and which might be due to the
underlying condition. They also saw cases where the patient was given the wrong
medication and it was incorrectly assumed by the patient they had been switched
to a different brand of the intended medication. And they note that medications
for spouses (or other family members sharing the same last name) may be mixed
up in pharmacies or at home.
In the long-term
care setting they note that patients are particularly susceptible to the
effects of multiple medications and that the elderly are more susceptible to
the harmful effects of medications for a variety of physiologic reasons. Here
also the means by which medications are administered may lead to the wrong
patient getting a medication. An example they give is one in which a medication
for one patient was put in the patient’s cereal. However, the patient was not
given the cereal immediately and another patient inadvertently ate the cereal.
They note that if this route is taken the medication should be mixed in with a
minimal amount of food and immediately given to the patient.
In the hospital setting, one variation of the multiple medications theme was patients taking medications they brought in from home. All hospitals must have strict policies for sequestering medications brought in from home or sending those medications back home with family or other caregivers. In those rare cases where a medication from home must be administered, it should be stored and dispensed by the hospital pharmacy and subject to all usual safety measures used by the hospital (barcoding, etc.). Another common problem they encountered in medication reconciliation is when only the labels from the medication bottles from home are read. Patients may be taking only half the dose that was printed on the label or taking one every other day or some other regimen. Another theme they see in hospitals is the incorrect dose theme, in particular related to verbal orders in which hear-back and read-back are not properly used. Lastly, the dose omission theme appears when a medication is intentionally or unintentionally left off a medication list. When the patient then transitions to another level of care the medication never gets restarted. They provide an example of a patient going through a withdrawal syndrome from such inadvertent discontinuation of a psychotropic drug. Such withdrawal symptoms may lead to misdiagnoses if the possibility of drug withdrawal is never considered. (See our August 30, 2011 Patient Safety Tip of the Week “Unintentional Discontinuation of Medications After Hospitalization” for an estimate of how often such inadvertent discontinuations occur).
In regard to the multiple medication theme it is important to note the tremendous increase in psychotropic polypharmacy in the past decade or so. One study (Mojtabai 2010) looking at office-based psychiatry practices showed that the median number of psychotropic medications prescribed at each visit increased from one in 1996 to two in 2006. These included many instances of patients receiving 2 or more antidepressants, 2 or more antipsychotics, or 2 or more sedative/hypnotics. The authors note that the evidence base for such combination therapy is often lacking. Moreover, off-label use of antipsychotics has also become very common (Leslie 2012).
There are also some unique problems with medication reconciliation and psychotropic drugs. For a variety of reasons patients may not reveal that they are taking such drugs. And even when you populate your medication reconciliation forms by downloads from your RHIO or from third party vendors like PBM’s psychotropic drugs are typically excluded because of specific legal confidentiality provisions.
While research into psychotropic medication errors and adverse events has been scant on the inpatient side, there has been almost no literature on the outpatient side. One paper (Maidment 2009) discusses some of the issues involved on the outpatient side. Some are service operational issues, such as delivery of behavioral health care across multiple transitions, with the associated problems in communication across providers, fragmented roles and responsibilities. As above, medication reconciliation is a process particularly vulnerable to error. The Maidment paper notes a study (Morcos 2002) in a mental health facility that demonstrated discrepancies in medication reconciliation in 43% of admissions and 69% of discharges. A second issue identified by Maidment et al. is the fact that many patients with mental health illnesses have multiple physical comorbidities and complex medication regimens. A third issue is the lack of training and familiarity with certain classes of medication. Many adverse drug events on behavioral health units are due to non-psychotropic drugs (eg. insulin) that the behavioral health staff is less familiar with. In the Rothschild study (Rothschild 2007) non-psychiatric drugs accounted for only 4% of the errors but they accounted for a third of the potentially preventable events on psychiatric units. Likewise, many of the psychotropic drug adverse events seen on general med/surg units likely reflects a similar unfamiliaritiy with those drugs. And that problem of unfamiliarity with psychotropic drugs is now extending to the primary care. And a fourth issue is the cognitive impairment and communications problems that may prevent a patient with mental health problems from helping avoid medication errors. More than that, levels of distrust between patients and professionals may further compromise the situation.
More and more, because of the shortage of psychiatrists nationwide, primary care physicians are managing more behavioral health conditions like depression. But in many cases they may be relatively uncomfortable managing some of the psychotropic agents needed. Many communities are adopting the DIAMOND model (ICSI 2007) for management of depression in the primary care setting. That model is based on the great work from the IMPACT study led by the University of Washington. That approach utilizes the PHQ-9 for both screening and monitoring outcomes, a stepped care approach for treatment modification and intensification, and use of care coordinators embedded in the primary care practices. However, one of the key elements is a regular interaction with a psychiatrist or other behavioral health provider. At those regular sessions specific questions about psychotropic drugs are often discussed.
We all know about the parkinsonian side effects, tardive
dyskinesias and other movement disorders plus sexual dysfunction and
orthostatic hypotension that may result from many psychotropic medications.
Obesity, insulin resistance, and the metabolic syndrome are some of the serious
complications of atypical antipsychotics. But there are multiple other
potentially serious complications of some psychotropic drugs that are,
fortunately, relatively infrequent. The best known are the neuroleptic
malignant syndrome and the serotonin syrndrome. In our June 29, 2010 Patient Safety Tip of the Week “Torsade
de Pointes: Are Your Patients At Risk?” we discussed how some drugs may
prolong the Q-T interval and lead to ventricular tachycardia. Our
October 2010 What’s New in the Patient Safety World column “Antipsychotic
Drugs and Venous Thrombembolism” noted that there is an increased risk of
venous thromboembolism with antipsychotic drugs, though the overall risk is
relatively low. And a recent
study (Jambet
2012) described a fatal abdominal compartment syndrome in 2 patients taking
multiple psychotropic drugs.
So are there interventions known to help minimize adverse drug events related to psychotropic drugs? A study (Jayaram 2011) in a hospital setting found that an error reporting system in conjunction with CPOE (computerized physician order entry), education, and continuous feedback on errors resulted in a significant reduction in such medication adverse events. Case ascertainment in that study was limited and it is not known whether the results can be applied to other settings, such as the outpatient setting, but the results are promising. Grasso and colleagues (Grasso 2003) also look to the promise of CPOE in preventing such errors but also point out the utility of the iPhone or other PDA you probably have with you now in providing useful information about these drugs. They recommend use of protocols or order sets, particularly for those drugs with narrow therapeutic windows, and use of decision support tools to identify other conditions (diagnoses or lab results) that might lead to changing orders for psychotropic drugs. And education of physician and nursing staffs and patients themselves are important.
To that we’d add the need to establish formal auditing when prescribing psychotropic drugs. For each you should have a formal protocol specifying which common side effects to look for and when to look.
We think that ultimately we’ll need more sophisticated monitoring programs, perhaps similar to how we use trigger tools, to monitor for both adverse drug events and medication errors. However, what is clear is that there is currently a paucity of high quality systematic studies on ADE’s and errors related to psychotropic drugs and how to prevent them.
References:
Rothschild JM, Mann K, Keohane CA, et al. Medication safety
in a psychiatric hospital. General Hospital Psychiatry 2007; 29(2): 156-162
http://www.sciencedirect.com/science/article/pii/S0163834306002222
Huybrechts KF, Gerhard T, Crystal S, et al. Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study. BMJ 2012; 344:e977 (Published 23 February 2012)
http://www.bmj.com/highwire/filestream/569706/field_highwire_article_pdf/0.pdf
ISMP Canada. Analysis of Harmful Medication Incidents Involving Psychotropic Medications. ISMP Canada Safety Bulletin 2012; 12(2): 1-5 March 6, 2012
Mojtabai R, Olfson
M. National Trends in Psychotropic Medication Polypharmacy in
Office-Based Psychiatry. Arch Gen
Psychiatry 2010; 67(1): 26-36
http://archpsyc.ama-assn.org/cgi/content/full/67/1/26
Leslie DL, Rosenheck R. Off-Label Use of Antipsychotic Medications in Medicaid. Am J Manag Care 2012; 18(3): e109-e117
http://www.ajmc.com/articles/Off-Label-Use-of-Antipsychotic-Medications-in-Medicaid
Maidment ID, Parmentier
H. Medication error in mental health: implications for primary care. Ment
Health Fam Med. 2009; 6(4): 203–207
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873876/pdf/MHFM-06-203.pdf
Morcos S, Francis
S-A, Duggan C. Where are the weakest links?: A descriptive study of
discrepancies in prescribing between primary and secondary sectors of mental
health service provision. Psychiatric
Bulletin 2002; 26: 371-374
http://pb.rcpsych.org/content/26/10/371.full
ICSI. DIAMOND
Initiative. Depression Improvement Across Minnesota. 2007
http://www.icsi.org/colloquium_-_2007/diamond_panel.html
IMPACT.
Evidence-Based Depression Care.
Jambet S, Guiu B,
Olive-Abergel P, Grandvuillemin A, et al. Psychiatric drug–induced fatal
abdominal compartment syndrome. American Journal of Emergency Medicine
2012; 30(3): 513.e5-513.e7
http://www.ajemjournal.com/article/S0735-6757%2811%2900014-3/fulltext
Jayaram G, Doyle D,
Steinwachs D, Samuels J. Identifying and Reducing Medication Errors in
Psychiatry: Creating a Culture of Safety Through the Use of an Adverse Event
Reporting Mechanism. Journal of Psychiatric Practice. 17(2):81-88, March 2011
Grasso BC,
Rothschild JM, Genest R, Bates DW. What Do We Know About Medication Errors in Inpatient
Psychiatry? Joint Commission Journal on Quality and Safety 2003; 29(8): 391-400
http://www.patientsafetysolutions.com/