The Intricacies of Antidepressant Interactions

Once upon a time there were jokes circulating about putting Prozac (fluoxetine) in the drinking water.

The idea was that the modern antidepressants were indicated for most people living in today’s society, and that these drugs were completely safe to use.

Now, these same drugs have so many warnings that they have become increasingly difficult to use in treating the common maladies of depression and anxiety.

The earliest scuttlebutt about Prozac causing suicidal thinking never did go away completely. We were assured that the suicide rate itself did not go up, only thinking about it. Some of that was explained by powerful antidepressants potentially unmasking bipolar illness and causing manic episodes. But a few years later, Paxil (paroxetine) was reported to cause suicidality in adolescents.

Just in the past few months, I was reminded several times about the intricacies of prescribing SSRIs.

A middle aged man on the blood thinner warfarin suddenly developed nosebleeds when his INR shot above the therapeutic range. His psychiatrist had doubled his Prozac two weeks earlier.

An anxious and depressed elderly woman wanted to try an antidepressant, and I gave her a low dose of Lexapro (escitalopram). She told me the following week that she felt tired and listless. I ordered some routine blood taste and her sodium level came back precipitously low. We stopped her Lexapro and she felt better again within a week.

A tall, thin elderly man with Parkinson’s disease and depression wanted to try something for his mood. I searched the literature and prescribed the SSRI with the most data on use in his condition. The following week he felt lightheaded. His blood pressure and pulse were both lower than his baseline, and I ended up cutting his beta blocker in half twice before his vital signs normalized; I had never heard or seen this interaction before.

A middle aged woman with a history of pulmonary emboli had been difficult to regulate on warfarin, and during a recent hospitalization, the doctors had changed her over to the novel anticoagulant Eliquis (apixaban), which doesn’t require any monitoring. When it was time to refill her Zoloft (sertraline), my computer flagged me with a bold, red warning that apixaban and sertraline are a dangerous combination resulting in increased risk for bleeding.

The list of warnings for this class of drug goes on, including effects on pregnancy, heart arrhythmias, seizures, glaucoma, liver disease and diabetes.

Given that their effectiveness is reported to be only marginally better than placebo, I have become increasingly more cautious about prescribing them.

Just this year, though, in Molecular Psychiatry, a new analysis of old data suggests that previous studies had used an ineffective rating system for depression, and that SSRIs are more powerful than we thought.

I remain skeptical. Once bitten, twice shy.

4 Responses to “The Intricacies of Antidepressant Interactions”


  1. 1 meyati May 28, 2016 at 2:06 pm

    Sometimes I don’t think that the practice of medicine has improved any. The doctors around here here have an arbitary cut off age around 68, where a patient can’t have pain killer other than a NSAID-acetaphinmen, can’t have a mild anything. My network uses 68 years old, as the guideline. They don’t want me to be addicted or fall. I’ve almost died from severe IBSD several times. The military successfully used Librax to stop one episode, and I took that unil November 2015, when the manufactorer stopped production. I’m living- I’m 74 years old-2 days ago my PCP and I talked about that if I have a really bad spell, that there isn’t anything that can be done. Sometimes my episodes were about 5 years apart, so who knows how long my stomach will keep working. Maybe by that time, there will be a replacement med-ha, ha, ha, She was trying to give me hope. The reality is that the ERs are useless-all they can do is connect me to IVs, and do an emergency colonoscopy-which has a 50% chance of killing me by infections, internal abrasions that start internal bleeding, or perforations. I tell my GI and all other doctors that I really, really don’t want to go to the ER, so my GI arranged for a phone consult, if several days of water doesn’t work. Biopsies identified seizure prone black areas in my GI system.

    In the late 1980s, a “think tank” gathered groups of people in different parts of the US. They were asked to rate ‘new’ inventions for safety. One of the new inventions ended up being natural gas that is piped into almost every American home. Only a few people said- “Whoa there! Isn’t that natural gas?” Almost all inventions were voted as being too dangerous to be used. The study was to test a reason why there seems to be a drop in inventions that make it to the market. I am wondering if this is the thought about current medicine. Nobody wants to get sick, no doctor wants to make anybody sick. I just know that I was going crazy from losing my depressent, I was going crazy from rage and despair that I can’t even get medical care based on the practice of good medicine that was used in 1960. Almost every day- I say to myself- I am alive-I am surprised-

  2. 2 Lisa May 28, 2016 at 6:26 pm

    Almost all antidepressants have the risk of inciting TdP. It’s not a huge problem for most people, but I am genetically predisposed to developing TdP and have to avoid the drugs that can cause it. But what happens when you have someone on escitalopram and they get bronchitis? You put them on albuterol. If it’s bacterial, you might put them on bactrim. Then they are taking multiple drugs that can cause TdP. How many drugs that can prolong the QT interval can a normal person be on before their QT interval becomes dangerously prolonged? It’s rare but consider Heath Ledger, it happens. Every drug has side effects. Multiplying drugs multiplies the danger from those side effects. Unfortunately, you are the one who must decide if the benefit is worth the risk.

  3. 3 Ellen Smith, MD, FAAFP June 30, 2016 at 6:58 pm

    I think the idea of a slow doctor is a fantastic one–not just slow at the end of life, but slow during all of life–slowly getting to know the patient and their issues, as well as patients slowly getting to know their doctor/patient.

    As for the antidepressant issue, I am aware that some studies show that they don’t work better than placebo, but experience shows otherwise for many. I understand that I can be biased and patients may tell me what they want to hear, yet I still think they help many.

    There is a new Genecept Assay that is based on one’s genes and gives ideas about what may work better and what may be more prone to side effects. I need to be upfront, I have not yet used it, because I am not currently seeing patients, but have thought about ordering one on myself. I have talked to colleagues who find it very beneficial. I see it similar to how I use the PHQ-9 and GAD-7 questionnaires–additional information to use along with, not instead of clinical acumen. When I return to practice I plan to use it.

    • 4 acountrydoctorwrites June 30, 2016 at 8:54 pm

      Gene sight data is proprietary so we don’t really know how good it is. Great money maker for the company….


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