Published in the December 2013 issue of Today’s Hospitalist
EVEN WHEN PATIENTS WITH psychiatric conditions are well-managed, psychologically stable and reliable historians, things can really go wrong for them in the inpatient setting. Hospitalists treating these patients may find themselves facing a crisis “and physicians may not understand what’s behind the problem.
Here’s an example cited by Leo Pozuelo, MD, vice chair of clinical psychiatry at the Cleveland Clinic and section head of consultative psychiatry, during a presentation at this year’s Society of Hospital Medicine meeting: A middle-aged patient with bipolar disorder comes out of breast reconstruction surgery and develops nystagmus in the recovery unit, along with jerking movements and some dystonia. Neurology is consulted for possible seizure, which was ruled out.
By day 2, she’s been moved to the hospital medicine unit. But the patient is so listless and weak that she can’t leave her bed. She continues to worsen, even though she looks good “on paper,” with normal creatinine and electrolyte levels.
Because the patient has historically been well-managed for years on 300 mg daily of lamotrigine and 450 mg lithium twice daily, those medications were continued pre- and post-op.
What was the problem? Her baseline outpatient levels were 0.6 to 0.7 and during the hospital they rose to 1.0 “still therapeutic, but high for her. The lithium was discontinued, as was the Phenergan she was receiving, because both contributed to her being sedated. Within 36 hours, she was doing well, up and about, and lucid.
“Lithium can produce a neurotoxicity predisposing patients to confusion or a delirium,” Dr. Pozuelo explained. “Lithium is a medication that I would discontinue right before surgery, then resume at a half dose after the patient has gotten through the surgery for a few days before returning to the full dose.”
Ideally, Dr. Pozuelo noted, hospitalists won’t be treating such psychiatrically complex postop patients alone, but there are plenty of cases when hospitalists have to deal with psychotropic drugs. In his presentation, Dr. Pozuelo provided guidance on how to use antipsychotics effectively. He also talked about the more common psychotropic drug classes hospitalists encounter: anxiolytics, antidepressants and mood stabilizers.
While most hospitalists have some experience prescribing or continuing antidepressants, Dr. Pozuelo noted some considerations that doctors should keep in mind with both older and newer agents.
One is that some older antidepressants “trazodone, in particular “are less commonly used now for treating depression. That’s because of the drugs’ sedative side effects and the large doses required (300 to 400 mg daily) for therapeutic antidepressant effect.
However, lower dosages of trazodone can help for sleep. “Doctors are comfortable using the 25 or 50 mg dose, based on decades of experience,” he said. “It certainly helps target symptoms of insomnia.”
In general, tricyclic antidepressants should be avoided in the medically ill due to their side effects. However, the picture becomes more clear with selective serotonin reuptake inhibitors (SSRIs), which have become the agents of choice for depression and anxiety disorders. With so many of these agents to choose from, Dr. Pozuelo pointed out that it’s hard to keep up with and to differentiate among them.
Fluoxetine, sertraline, paroxetine, escitalopram and citalopram are the most commonly prescribed SSRIs, he said. He and his colleagues tend to start patients on sertraline, escitalopram or citalopram.
“To some degree, these SSRIs are all interchangeable, but we tend to go with these three when we are prescribing de novo because there are fewer drug-drug interactions,” said Dr. Pozuelo.
As for dual-acting antidepressants that deal with serotonin and selective norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine, duloxetine and others such as mirtazapine, these agents are well-tolerated. But if hospitalists are concerned about sparking serotonin syndrome, the tried-and-true alternative is Wellbutrin.
“It doesn’t tickle the serotonin, but works by the dopamine with some epinephrine kick,” he said. “It gives you a bit of ease in that category, although it is not the frontline in treating anxiety.”
Dr. Pozuelo also offered the following reminders for hospitalists prescribing antidepressants:
- When using mirtazapine(15,30mg), have patients take it at night because it’s sedating. And in patients with GI issues, the drug can effectively combat nausea. That can be an extra bonus in some cases as mirtazapine has the same mechanism of action as ondansetron, and is made in a dissolvable form for patients having difficulty with oral intake.
- Because duloxetine can cause nausea, start with the 30 mg (not the 60 mg) dose, then ramp the dosage up over a few days if it’s tolerated.
- When considering bupropion (Zyban) for smoking cessation, the full therapeutic dose of 150 mg BID can provoke anxiety. “Patients can get a bit wired,” Dr. Pozuelo said, “so start them off with a lower dose.”
- The only available transdermal antidepressant is Emsam (from selegeline, which is used in Parkinson’s medications). The drug comes in 6 mg patches and can help patients who cannot tolerate oral medications. It does not have food interactions at this dose.
- Don’t add paroxetine to tricyclics in patients already taking tricyclics for sleep or diabetic neuropathy; paroxetine is a potent 2D6 inhibitor that can elevate tricyclic levels and create a life-threatening situation. “This is something we’re always on the patrol for in drug-drug interactions,” said Dr. Pozuelo. “In general, we also avoid use of tricyclics due to their cardiac side effects”
- Concerns about QT elongation with citalopram warrant keeping the dose to 20 mg or lower in cardiac patients.Dr. Pozuelo also noted that serotonin syndrome is usually seen in patients “accumulating medications “antibiotics, SSRIs, buspirone and triptans “that just flood the neuro and GI systems.” The best way to treat it is to withdraw the offending agents and use conservative benzodiazepine treatment to counter any associated anxiety.
The good news is that the syndrome usually resolves within 24 or 48 hours because most SSRIs have a short half-life. The exception is fluoxetine, which has a half-life of about five days.
With anxiety disorders the most prevalent psychiatric disorder, hospitalists encounter plenty of patients with the condition. While psychiatrists tend to prescribe lorazepam or clonazepam for this population, Dr. Pozuelo noted that primary care physicians are more likely to prescribe benzodiazepines such as alprazolam because they’re more familiar with them.
What doesn’t work for acute anxiety, said Dr. Pozuelo, is a drug that’s been touted for its more favorable dependence profile: Buspar. “As innocuous as it sounds “and it isn’t habit-forming “it’s absolutely useless for perioperative management of anxious patients because it takes two to three weeks to kick in,” he explained.
When patients are NPO in the hospital setting and cannot receive their home benzodiazepines, Dr. Pozuelo recommended the following equivalent oral doses for switching patients and avoiding withdrawal. Keep in mind, he noted, that IV doses are twice as powerful as oral ones:
- Librium: 10 mg
- Valium: 5 mg
- Ativan: 1 mg
- Klonopin: 0.5 mg
- Xanax: 0.25 mg
“We rarely use Valium IV,” he said, “but instead use Ativan IV to hold over perioperative patients so they won’t experience withdrawal.” And in patients being started on antidepressants de novo for combined depression and anxiety, an overlap with benzodiazepines can be helpful because it takes two to three weeks before the antidepressant effect kicks in.
In the setting of alcohol withdrawal, benzodiazepine coverage is the norm. For patients in whom benzodiazepines are contraindicated, Neurontin “in 300 to 600 mg TID dose “may be an effective alternative. As for patients going through severe alcohol withdrawal that is refractory to benzodiazepines, Dr. Pozuelo suggested using a Precedex drip, which has to be administered in an ICU.
“In cases where the alcohol withdrawal is advanced and that horse is out of the barn,” said Dr. Pozuelo, “placing the patient on a Precedex drip can help.”
Mood stabilizers and antipsychotics
Patients with bipolar disorder comprise only about 5% of the population (compared to 15% to 20% for anxiety disorders). But hospitalists are still likely to care for patients with bipolar disorder, who can present with management issues. Protecting their sleep is one key intervention.
Because these patients have demonstrable highs and lows, many take mood stabilizers like valproic acid, carbamazepine or lamotrigine. With valproic acid, hospitalists should remember to check ammonia levels, which may increase, and platelet levels, which may drop. With carbamazepine, hospitalists should check CBC values and sodium levels. It is not uncommon, Dr. Pozuelo noted, for bipolar patients to be on two or more maintenance medications.
Lamotrigine is one of the few mood stabilizers that is dose-dependent in terms of its risk (for Stevens Johnson syndrome, notably). If the home dose is missed for a significant period of time “more than five to seven days ” doctors should titrate it back slowly after curbsiding a consultant or pharmacist on how to do this.
Lithium remains a true-blue mood stabilizer, with many bipolar-disorder patients doing well on the drug for long periods. But due to its neurotoxicity and propensity for delirium, it is probably the only bipolar medication to hold the night before surgery and for a couple of days afterwards. Otherwise, it is important to restart bipolar patients’ medications as soon as possible perioperatively.
Antipsychotics “such as Zyprexa or Seroquel “are used in bipolar patients to ensure sleep and stabilize mood. “Even though you can’t restart some of the classic mood stabilizers perioperatively, in the short term you can probably get away with using an antipsychotic just to keep the patient stable,” Dr. Pozuelo said. He added that hospitalists will ideally be choosing a drug in conjunction with a psychiatry consult team.
Schizophrenia is even rarer than bipolar disorder, affecting only between 1% and 3% of the population. But these patients also require special handling in the hospital, with hospitalists ending up doing primary management and using antipsychotics. Antipsychotics are also used for managing delirium and, in baby doses such as 25 mg TID of Seroquel, for anxiety control in patients who cannot take benzodiazepines.
The classic antipsychotic, haloperidol, is still effective for delirium and has the additional advantages of being neither hypotensive nor anticholinergic. And it’s not sedating, said Dr. Pozuelo, “like Seroquel (quetiapine) or Zyprexa (olanzapine).”
As for dose ranges, Dr. Pozuelo reminded the audience that 0.5 mg IV q8 of haloperidol would be equivalent to an oral dose of 1 mg. The best strategy is “early and frequent dosing, in effect a ‘marinade’ that produces enough dopamine blockade to symptomatically turn around a delirium.” But he cautioned against using clozapine, a second line or third line drug for schizophrenia, to alleviate delirium. That’s because it’s anticholinergic as well as extremely antihistaminic and hypotensive.
Dr. Pozuelo also clarified the indications for a drug seen on commercial TV: aripiprazole (Abilify). Although it’s being marketed for depression augmentation and used in bipolar disorder, it’s actually a potent antipsychotic approved for schizophrenia “but in that category, it can cause nausea and akathisia, making the patient feel restless. Its potential advantages are that it is not sedating and doesn’t have a detrimental effect on the QTc.
If hospitalists are looking for a sedating effect in this antipsychotic category, Dr. Pozuelo recommended quetiapine and olanzapine over ziprasidone (Geodon) or aripiprazole. He also noted that the big division between the typical antipsychotics and the newer atypical ones is that the typical drugs worsen extrapyramidal (EPS) symptoms.
Typicals vs. atypicals
When asked what hospitalists might see in patients withdrawing from antipsychotics, Dr. Pozuelo explained that the physiologic effects are minimal, especially when compared to drugs like benzodiazepines or alcohol or even antidepressants. However, patients off the drugs for a significant period of time may start having delusions or hallucinations. In general, hospitalists need to keep in mind that they should restart a psychiatric patient’s medication as soon as possible.
“When medications for a schizophrenic or bipolar patient cannot be restarted, we rely on oral dissolvable tablets of Zyprexa or some IV haloperidol to hold them over in the interim,” he said.
Dr. Pozuelo also offered advice on choosing between typical and atypical antipsychotics: Patients with cardiac conditions are usually better candidates for the atypical drugs because of typicals’ known QT prolongation. However, ziprasidone should not be used in cardiac patients or those at risk for QT prolongation.
All patients on antipsychotics should have EKG monitoring. And the atypicals are generally preferred for patients with Parkinson’s because they don’t worsen EPS symptoms. “Quetiapine,” said Dr. Pozuelo, “has the best profile in this regard.”
Bonnie Darves is a freelance health care writer based in Seattle.