Mast Cell Disease & Depression: Is Doxepin The Answer?

The Treatments / Thursday, February 2nd, 2017 / no comments

Chronic depression in mast cell disease patients is frequently seen both in mastocytosis and mast cell activation syndrome.

When you understand the way mast cell disease works it’s easy to see why we as patients sometimes battle clinical levels of depression, among (many) other things.

As a patient myself I have struggled off and on my entire life with bouts of depression. Sometimes it reaches the level of clinical depression but most of the time it’s low-level stuff,  just under the surface, keeping me feeling, well, “low”.

Over the years I tried many different medicines for depression, they were all SSRI’s and none of them worked. In fact, they all made me sicker the longer I used them, which is typical with so many medications and this disease, unfortunately. In fact, the Mastocytosis Society states unequivocally:

Antidepressants – Mastocytosis patients have reported adverse reactions to all types of SSRI antidepressants. They should be avoided

It wasn’t until my diagnosis that I learned why I personally should avoid SSRI’s. But that doesn’t seem to be the case for everyone, I learned. From the incredibly informative website, I found this:

Treatment of neuropsychiatric symptoms in mast cell patients can include a variety of medications.  SSRI medications can reduce fatigue and depression in some inflammation models.  Some mast cell patients take these medications, usually with low starting doses in case mast cell degranulation in these people has conversely led to higher serotonin levels.  Bupropion, SNRIs and tricyclic medications are also commonly used for depressive symptoms in many chronic illness populations.


Some tricyclic antidepressants have antihistamine properties, with doxepin being a common choice.  Another tricyclic, amitriptyline, can inhibit release of mast cell mediators. Mianserin and mirtazapine can be prescribed for insomnia but also have antihistamine properties. Aprepitant could potentially be used in treatment of depression and cognitive impairment in mastocytosis and MCAS patients. Prochloperazine also decreases mast cell mediator release. Amantadine has improved depression and fatigue symptoms in multiple sclerosis patients. Inhibition of TNF with infliximab has improved depression in patients with high levels of inflammation.

Dr. Afrin also talks about using SSRI’s successfully in his book I’m reviewing (I’ll get to that chapter soon right here in my series). So apparently some of us can take SSRI’s with very good results, the same way some of us can use NSAID’s while other can’t, I suppose. The reasons why are unclear. I happen to be in the category that can’t tolerate either.

I did notice that at the end of the text I quoted above, Lisa mentions infliximab as a TNF inhibitor and antidepressant in patients with high levels of inflammation (me!), and if you read my post on granuloma annulare you would know that I feel there is a pretty clear link between that disease and my mast cells dumping TNF so I wondered if infliximab could be a good match for me.

Then I looked up the price:

In the United States, Remicade/infliximab can cost $19,000 to $22,000 a year per patient, according to Centocor in 2007.

Yikes! I definitely can’t afford that, even with insurance it would still probably be far too expensive.

I have found relief, however, by taking low doses of Doxepin. I am taking 10mg morning and night and I definitely feel a difference in both the depression and also in my overall histamine response. It helps me sleep better at night and I wake up to find I don’t have to run to the medicine cabinet right away. Before Doxepin I was waking up and degranulating almost immediately but not now.

**9/2017 edited to add: I have stopped taking Doxepin and my other antihistamines. You can read why here.

I first found Doxepin listed at the Mastocytosis Society website:

Doxepin – Research has proven (and patients have reported) that this medication may cause heart arrhythmias in some at high doses (over 50mg). We take it in very low dose (eg.5-10mg) and slowly increase under Physician guidance. This drug is effective for mastocytosis patients in low doses. Histamine and other chemicals are dumped by our mast cells during sleep. Taking Doxepin at bedtime is an effective antihistamine with the rare ability to cross the blood-brain barrier. It helps with all symptoms.

I’ve read other anecdotal stories of MCAS patients finding it helps them with more than just depression. It’s described as a:

Nerve pain medication and antidepressant
It can treat depression, anxiety, and sleep disorders in its oral form. When applied topically, it can reduce itching caused by atopic dermatitis, lichen simplex chronicus, and other skin diseases.

I like that it is useful for treating nerve pain, because I definitely have a lot of that when I’m flaring. So overall, I’m happy with the Doxepin and it seems to be helping with just about everything, just like the experts said. The longer I’m on it the more clearly I can see that it’s a valuable addition to my medicinal regimen for my own MCAS and I am thankful I found it. Best of all, it’s relatively inexpensive for me.

Of course, we are all very individual so what works for me may not work for you but if you find that SSRI’s trigger you then Doxepin may be the answer. As always, talk to your doctor if you believe you have mast cell disease or any disease or if you are already diagnosed and want to try a new medicine. These are just my own personal experiences with mast cell disease but I’m happy to share them in case they help someone else out there.

Remember, we’re in this craziness together.


xo Michelle Dellene

Mother. Wife. Patient. Keeper of Huskies. MCAS blogger & advocate. Living life in the mast lane with the Grand Tetons & Yellowstone as my backyard. You can also find me blogging at Life In The Mast Lane and The Empty Nest Housewife.

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