Paroxetine—otherwise known by the trade name Paxil—is generally not your best friend on the hospital medicine service, according to Leo Pozuelo, MD, FACP, section head of psychiatric consultation at the Cleveland Clinic, who spoke about psychotropic drugs at Hospital Medicine 2013 in National Harbor, Md., in May.
Consider this scenario, which “happens once a month at our hospital,” said Dr. Pozuelo. A patient with cardiac disease and diabetic neuropathy is given amitriptyline—a tricyclic antidepressant—to alleviate pain and promote sleep. The patient is still depressed secondary to his clinical condition, however, and so is given paroxetine.
“Paroxetine is a huge inhibitor of cytochrome P450 2D6, so that 25 mg or 50 mg of tricyclic with the paroxetine on board skyrockets and tips over into a toxic range,” Dr. Pozuelo said. “This is something we are always on the patrol for, so keep it simple. If you have to prescribe an antidepressant de novo, in the medically ill, don't use paroxetine.”
For antidepressants, the Cleveland Clinic psychiatry consult service favors selective serotonin reuptake inhibitors (SSRIs) like sertraline (Zoloft), citalopram (Celexa) and escitalopram (Lexapro) because they have no major drug-drug interactions. The caveat is using the citalopram (Celexa) in lower dose range of 20 mg or less. The non-SSRIs venlafaxine (Effexor), mirtazapine (Remeron), and bupropion (Wellbutrin) are also “pretty good” and lack significant interactions, Dr. Pozuelo added.
Monoamine oxidase inhibitors (MAOIs) have significant drug-drug and dietary interactions, however. “We tend to avoid these like the plague,” Dr. Pozuelo said.
Most valuable players
Most antidepressants are similar in efficacy, so the choice among them is mostly about tolerability, interaction effects and side effect profile, Dr. Pozuelo said. “So, for example, when it comes to tricyclics, they tend to be sedating, more anticholinergic, and hypotensive, which is typically why we don't prescribe these as first line in the medically ill,” he said.
Mirtazapine is a favorite of his consult service, in part because it has a sedating effect and reduces nausea. “When I am on the colorectal service in particular, I am actually looking for reasons not to prescribe this one in patients who are clinically depressed. It helps with nausea (works just as Zofran [ondansetron] does) and gets the patient into a good sleep cycle,” Dr. Pozuelo said.
Mirtazapine is given once a day at night, and the antidepressant range is 30 to 45 mg, he added. Starting off at 15mg is a good idea to gauge tolerability.
Duloxetine (Cymbalta) is particularly helpful for patients with pain syndromes, he said. One caveat is that this medication can cause nausea if started at a full 60-mg dose off the bat. Best to start at 20 to 30 mg and titrate up after a few days and to administer the drug with a meal, Dr. Pozuelo said.
For pain patients, “norepinephrine is the key to treat the pain,” so serotonin- norepinephrine reuptake inhibitors (SNRIs) are a good bet, he said. In addition to duloxetine, consider venlafaxine, desvenlafaxine (Pristiq), and milnacipran (Savella)—though the latter is only FDA-indicated for fibromyalgia.
It's important to remember that while the side effects of antidepressants often kick in soon, the antidepressant action itself can take two to three weeks to be effective. “Sometimes we forget this in our busy hospitalist service, when we want to treat depression and anxiety. Keep in mind the timeline,” he said.
Cardiac, stroke and gastric bypass patients
In depressed cardiac patients, the SSRIs have a “proven safety profile,” Dr. Pozuelo said. Two randomized controlled trials have established the safety and efficacy of sertraline and citalopram in particular in this population, he said. “Again, the recent FDA advisory about citalopram and prolonged QTc guides us to keep the dose 20 mg or less in cardiac patients. So due to the above and in avoiding the drug-drug interactions of fluoxetine (Prozac) and paroxetine (Paxil), we now tend to prescribe sertraline (Zoloft) or escitalopram (Lexapro) more frequently in cardiac patients,” he said.
Bupropion also is safe for cardiac patients, as is mirtazapine. The latter will address anxiety as well as depression but can lead to weight gain. Duloxetine is also dual-acting on depression and anxiety, but there may be a mild interaction with beta-blockers, he noted.
If you use venlafaxine, be sure to monitor blood pressure, as case reports have indicated a lower defibrillator threshold for cardiac patients on this drug, he said. Finally, avoid tricyclics. “There is enough data about patients on tricyclics having a higher incidence of mortality that there is no reason to use them with cardiopaths,” Dr. Pozuelo said.
Patients who have had a stroke have a 25% risk of depression, and treating depression early will help facilitate rehabilitation, Dr. Pozuelo said. In general, avoid anticholinergic agents with stroke patients (for example, tricyclic antidepressants or benign appearing diphenhydramine [Benadryl], which is also anticholinergic), as they predispose to delirium, he said.
Stimulants can help stroke patients with initial psychomotor slowing, as well as with poor appetite, he said, but be aware this is an off-label use. Methylphenidate (Ritalin) at 2.5 mg twice daily (one dose in the morning and one in the early afternoon), with a few days' titration to 5 mg and then 10 mg twice daily, “hits the mental energy and helps with rehab. Patients mentally perk up, and their appetite perks up as well,” Dr. Pozuelo said.
Another patient population of note is gastric bypass patients, in whom bioavailability to psychotropics is impaired after surgery. It's a good idea to use liquid preparations or crush pills and to use immediate-release instead of extended-release formulas, Dr. Pozuelo said. Also, break dosages into multiple administrations throughout the day, and be aware you may need to use higher dosages in the early postoperative period, when bioavailability is the worst, he said.
Patients with anxiety
Patients who present with depression and comorbid anxiety should have the main antidepressant medication—usually an SSRI or dual-acting antidepressant—titrated upward slowly to decrease agitation. If you give them the full therapeutic dose of the antidepressant from the beginning, this can cause jitteriness, and you will lose compliance with the patient. In the first weeks, you can add a short-term benzodiazepine to provide immediate relief from the anxiety. Appropriate dosages include lorazepam, 0.5 to 1 mg twice daily; clonazepam, 0.25 to 0.5 mg twice daily; or alprazolam, 0.25 to 0.5 mg three times daily, Dr. Pozuelo said.
Be aware that there is abuse potential with these anxiolytics, and there is overdose potential as well and therefore the benzodiazepines are generally used short-term, he said. But don't be too apprehensive about these medications. “The hospital is the epitome of loss of control, so whatever anxiety a person had outside the hospital is going to be magnified in the hospital,” he said. “You can recommend psychotherapy and hypnosis, but in acute devastating anxiety, listen: Xanax can be a good friend.”
Perioperative patients who come into the hospital on a regimen of benzodiazepines need to be handled with care. Oral equivalencies can be helpful to switch patients from their home regimens to in-house medications when needed. In a nutshell, there are some oral equivalent guidelines: 10 mg of chlordiazepoxide (Librium) = 5 mg of diazepam (Valium) = 1 mg of lorazepam = 0.5 mg of clonazepam = 0.25 mg of alprazolam.
Remember that the intravenous (IV) form of benzodiazepines is twice as powerful as oral tablets. This means, for example, that 1 mg of lorazepam by mouth is the same as 0.5 mg IV, Dr. Pozuelo said.
Other tips Dr. Pozuelo offered during his talk include the following:
- Avoid bupropion in depressed patients with comorbid anxiety, as it tends to be anxiety-provoking.
- For patients who can't take medication in tablet, capsule or liquid form, the sole transdermal antidepressant is selegiline (Emsam), an MAOI. Stick with a dose of 6 mg per 24 hours, because at higher doses there are many drug-drug interactions. Also, wait two weeks after discontinuing this drug before starting a different antidepressant.
- Keep on the lookout for serotonin syndrome, i.e., too much serotonin. This syndrome can be triggered by (combination of an antidepressant with?) a non-antidepressant that's started in the hospital, such as a triptan or the antibiotic linezolid. The syndrome presents with agitation or restlessness, diarrhea, nausea, vomiting, overactive reflexes, and elevated blood pressure and heart rate. To treat, remove the offending agent, monitor, and prescribe benzodiazepines to deal with anxiety, if needed.
- Patients who've had antidepressants stopped perioperatively may experience discontinuation syndrome, which is characterized by dizziness, tremors and anxiety. It's a particular risk for patients who were taking paroxetine or venlafaxine. The syndrome is not life-threatening, however, and benzodiazepines can help take the edge off.
- Most bipolar disorder patients can be managed short-term in the hospital with an antipsychotic, in order to keep them stable. It's most important to protect sleep in these patients; to do so, you can use sedating antipsychotics like quetiapine fumarate (Seroquel) or olanzapine (Zyprexa).
- Haloperidol (Haldol) is still one of the most effective agents for delirium, as there is no hypotension or anticholinergic effect, and it's not sedating.
- For schizophrenia, clozapine is “the best antipsychotic out there,” Dr. Pozuelo said. It does have a “massive” side effect profile, which includes hypotensive, anticholinergic and antihistaminic risks. It also carries a seizure risk at high doses.