What To Do For Difficult To Treat Depression

Our pharmacist answers the latest question regarding what to do for difficult to treat depression.

Sep 27, 2017

Dwightnoi asked

Until 5 months ago, I had been taking Paxil for about 15 years for. the treatment of anxiety and depression. With my doctor's approval, I weaned myself off it over a 4 month period, taking a small dose of Prozac for the last 2 weeks of weaning in order to reduce possible withdrawal effects. The reason that I wanted to go off the Paxil was that I felt as though my emotions were frozen and I felt apathetic.No energy and no motivation to do anything other than sleep and read. I lost 3 relatives in the two years prior and couldn't even cry even though I felt a lot of grief. Regardless, after just a short time off all the medication, I'm not doing well at all. Nervous, general malaise, early morning awakening, deep sadness, excessive sleeping during the day, crying at the drop of a hat, craving carbohydrates, just had to double my Olmetec medication because my blood pressure rose to 159/92. I'm also negative and intolerant. I can't afford to feel this way because I'm caring for my husband who has Alzheimer's Disease. Besides, who want to feel so miserable. I know that I need to talk to my doctor about resuming the use of some kind of antidepressant anti anxiety medication. However, he's young and not that experienced in the use of psychotropic drugs. I need an expert opinion. Does Prozac work as well as Paxil? I like the idea that it has a shorter half life than the other SSRI's. My husband is on Zoloft, Aricept, and a tranquilizer (to control rages). Is Zoloft better for seniors (I'm 68)?

Answer

You're certainly in a tough situation but I will help as best I can.

Surprisingly as long as the SSRI drugs have been out, there really hasn't been any solid comparative trials that test one SSRI against another. There just is no incentive for a manufacturer to do such trials.

The first thing you and your doctor would need to tackle is why the Paxil (Paroxetine) was ineffective. Was your dose not optimized? Did Paxil work initially but begin to lose effect? This is actually quite common and typically a change in medication in the same class or to another class may be beneficial. It's really tough to give you a precise answer since I don't know your medical history, but I do have some suggestions for you.

The goal of depression treatment is obviously remission, i.e., all depressive symptoms are resolved. It is EXTREMELY common for patients to either have a bad response to antidepressants or have a diminishing response over time. In fact, studies have stated that around 30% to 46% of patients with depression do not have good response to initial therapy with antidepressants. Higher doses of drugs  may be an option, but this risks more frequent and severe adverse effects.

One strategy for difficult-to-treat depression is combination antidepressant therapy. Continuing the first antidepressant and adding a second, usually with a different mechanism of action, has the advantage of continuing the drug that produced a partial response and avoiding antidepressant discontinuation, or withdrawal symptoms.

Switching to a different antidepressant is another approach. This switch may be to another drug in the same class or a medication with a completely different mechanism of action. Patients who don't respond well to one SSRI may respond to another. In fact, and here is another interesting statistic,  42% to 71% of patients tend to respond to taking a second SSRI after subpar response to a first. However, response to a second SSRI is more likely when the first SSRI is poorly tolerated than when the patient is poorly responsive. Since you were on Paxil for 15 years, you may benefit more with a switch to a different class of medication altogether.

Below of some common antidepressant medications that work differently and may have a better effect for you:

SNRI drugs: SNRI work on two different neurotransmitters, serotonin and norepinephrine. Common examples of drugs include Cymbalta and Effexor. These have shown to have a fairly good benefit in patients and are usually not associated with the mood depression that some SSRIs can cause.

Wellbutrin (Buproprion) works as a dopamine agonist. This medication, like SNRIs is not usually associated with mood depression, quite the opposite in fact. This may be a good option for you.

After these drugs, there are certainly more last line options that work very well, but are associated with more serious side effects:

  • MAOI drugs
  • Clozapine
  • TCA drugs

The bottom line is that there is little research to define whether high antidepressant doses, combination therapy, or switching therapy is best. Therapy changes should be guided by the prescriber's judgment of the method most likely to achieve remission of depression.

In terms of your last question regarding Zoloft in the elderly, the whole SSRI class as a whole is the first recommendation in the elderly for depression. They are generally safe and well tolerated. There is something known as the Beers list which is a list of medications that are potentially inappropriate in the elderly. There are no SSRIs on the list.

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