Most of you who regular readers of this blog do not have to worry about this issue. But psychiatric patients are at greater risk of having Hep C. While 2% of the general population has Hep C, 20 % of persons with severe mental illness have Hep C. Regardless, any patient who faces treatment for the virus must also consider what is for many the most frightening side effect of interferon treatment–depression. Not everyone who is treated develops symptoms of depression that meet DSM-IV criteria for depression, but a significant proportion does. Data from various studies show that the rate of depression runs from 21% to 58 % with major depression developing at a mean of 12 weeks (range of 1 to 32 weeks). And those who don’t develop full syndromal criteria for Major Depression can struggle with subsyndromal depression. Manic symptoms such as elevated mood, irritability, insomnia, increased speech, racing thoughts etc can also emerge during treatment. Suicidal thoughts are concerningly high as well, effecting as many as 43% of patients in one study. Interestingly, however, not all studies have shown a correlation between previous psychiatric symptoms and the emergence of mood symptoms during Interferon treatment. In patients with a previous psychiatric history, the most common psychiatric side effects of treatment with interferon/ribavirin are irritability and anxiety (in 33-45%), insomnia (in 30-40%), depression (in 20-31%) and impaired concentration (in 10-17%). Aggressive behavior, psychosis and suicide was seen in less than 1%.
The mechanism behind the development of mood symptoms is not clear. It may possibly decrease CNS tryptophan level by disrupting the mechanism by which this serotonin building block is transported across the blood-brain barrier. Decreased serotonin would result in symptoms of depression and irritability. It may also act to disrupt central hormonal feedback systems or more directly alter neural functioning.
Should a prior history of psychiatric symptoms or fear of psychiatric complication prevent you from seeking treatment for Hep C. ABSOLUTELY NOT. When indicated, antiviral treatment should proceed. It is suggested that patients who have a past history of depression or are experiencing symptoms of depression should be put on antidepressants prophylactically to prevent treatment emergent worsening of their symptoms. While studies have shown that Celexa and Paxil are safe and effective, most antidepressants seem to be as well. I have used the SSRI’s and the dual-acting agents (Effexor and Cymbalta) and have also used Wellbutrin as an augmenting strategy in patients with resistent symptoms and/or a great deal of fatigue/concentration loss. It is really about being reasonably cautious. I would suggest that any patient who enters antiviral treatment should be seen by a counselor on a regular basis for the first few months (at least) of treatment. Regular screening for mood symptoms should occur and there should be a low threshold for referring a patient for a psychiatric consultation. Antiviral treatment for Hep C is so important for long term managment of this illness that psychiatric issues, or fear of psychiatric issues, should not be allowed to get in the way.
My thanks to Drs Martin, Krahn, and Balan and Rosati CRNP for their article in the November 2006 issue of Current Psychiatry from which the above statistics are derived.
–Dan Hartman, MD
Thank you for this message. Please write to let me know where I can get more information about how depression works on the individual who has suffered through treatment of Hep C . I nearly took my life while I was undergoing treatment. I have noticed that the depression grew after I was off the treatment (I had to get off treatment after 14 weeks) and it is till prevalent today. This is 10 months later. The depression mood is not as oppressive as it was before, and I am not on any anti-depressants at thsi time. I am also concerned about the corrrelation of ALT etc. levels in the blood. I was told that unless I had high levels I would not receive treatment. My levels were never high, but I did get very ill after the diagnosis. When I look back I can see that over the 30+ years it went undiagnosed I was gravely ill many times. Please help me talk to my Dr. about the actual numbers and the symptoms I am feeling now. I still have very sore joints, fatigue, sweats, memory trouble, shaking or trembling in my body, along with headaches which are still severe. My last blood work showed that my enzyme levels were within the normal range. The liver clinic said they would not treat me again, but they would put me on the transplant list. My depression and reaction to the treatment brought out other medical symptoms, so now I’m not just fighting hep c but I have a number of other illnesses with it. Hope you can help.
In my limited experience with patients who receive interferon, your reaction is not unusual. My concern is that you continue to experience symptoms of depression and, from what you say, are receiving no treatment for it. I would strongly urge you to get into treatment with a good therapist that can function as a life trainer for you (give you suggestions, follow through with you on practical interventions, etc) and would get under the care of a good psychiatrist who will aggressively treat your depression with medication. This is important for you here and now, but also in the future as you battle this liver ailment–your chances for medical success go up if you are not depressed. If you are not sure of where to get a good psychiatrist, talk to the GI people and ask who other patients use for these issues. Some of my patients with these issues are very sensitive to medications and require a little finesse with the medications (for example, low doses of multiple medications).
–DH MD
How do you feel about cymbalta? It worked great for me! But i did not want to take it after i learned about the FDA warning about chronic liver disease and Cymbalta?? How do you feel about that?
The word from the FDA is that, in a limited trial (6 patients diagnosed with cirrhosis who had “moderate liver impairment”) showed reduced clearance of Cymbalta compared to normal controls. The patients with liver disease had duloxetine clearance of 15% that of the controls and 5 fold increase in “AUC”. This is a fancy pharmacokinetic term meaning “area under the curve”. When they administer a drug to subjects and measure the blood level of the medicine over time and then plot it on a graph, you get a curve–like a bell curve if you are familiar with that. They can then calculate the area under the curve and it gives an indication of the overall exposure of the patient to the medicine. Interestingly, the Cmax (the maximum concentration of the medicine) did not increase with these patients, only the clearance rate–the half life was three times longer. So, people did not have “toxic levels” of the medicine but had a greatly reduced clearance.
What does this mean? I’m not sure. I don’t know if studies have been done on other antidepressants cleared by the liver (such as the SSRI’s). The culprit here is probably the 2D6 liver enzyme system that is highly effected by other medicines and by liver disease. When that is effected, Cymbalta is not cleared as quickly. Most of the SSRI’s do not get cleared by the 2D6 system so that they would be a better option . . . as long as they work. In the case of a patient with significant liver disease, I would probably not use Cymbalta as a first line agent (or even a second line agent) and, if I really needed to, would be in contact with the GI doc and would use very low doses.
For someone who has Hep-c and the liver biopsy came back, Stage 1 grade 1, and the SSNRI work best for the patient, what would you say between cymbalta and effexor? Also i understand the above reply. So how did the fda come to the conclusion that cymbalta could make underlying liver disease worse?
I have been on prophylactic prozac for a good portion of my treatment (friday will be week 23) and last week had onset of some strange thinking (very negative…i.e., no one cares for me, etc.). This is very unusual for me. I spoke to my internist and he doubled my prozac to 20 vs. the 10 i had been taking.
Is late onset subclinical depression and altered thinking normal for treatment? (180 pegasys, 1400 riba). I am also now hyperthyroid since about week 20.
If it is germane, I was infected last november during surgery for a 20 cm ovarian cyst, no malginancy, progressed to acute hep c eight weeks later (active hepatitis, lfts 800s 700s) and then started treatment at month four postinfection. I’m considered acute. Does that explain the late onset?
Otherwise counts are quite good.
What you bring up is the value of therapy–even maintenance or infrequent therapy–for patients who have chronic medical issues. What you describe is not necessarily abnormal. You need to remember that the normal range of human experience includes periods of profound self doubt and feelings of isolation. They can be a symptom of depression . . . or a symptom of being human. When one is subjected to the crisis of serious medical illness there is a variety of reactions to it. You have, by your brief description, mashalled your internal resources and have been generally strong. It is typical (and normal) for people to have episodes of dispair and sadness when confronted by medical issues. Hashing out the dis-ordered thinking (negativistic, self-doubt, etc) with a therapist who knows you can be very beneficial and sometimes enough to avoid additional medication. Is it unusual to have a late onset of depression symptoms? Yes, but not unheard of. Given your brief description, I cannot assume that the negativistic thinking is part of a depression, necessarily. It could be part of the process of your development through the stages of dealing with this illness. That said, I think there is no harm in bumping up the prozac to 20.
I hope all goes well for you.
–DH MD
Matt–
Sorry for the delay in my comments. Back from vacation and all. If SSRI worked best for the patient, why are you even considering the use of Effexor or Cymbalta. A great deal of medication difficulties with psych meds come from not using our seventh sense–common sense. If an SSRI worked best, stick with what worked–an SSRI. Now, you don’t give much information, so lets assume that an SSRI is NOT good for you. Given the info about Cymbalta, Effexor may be a better option for your (tho’ please see my comments about the warnings about Cymbalta above). Most importantly, have you talked to your shrink about this???? You sound like you have significant questions the they should (of course) be directed to the doc prescribing the meds.
–DH MD
Dr. Dan:
Thanks for the feedback. I’ve gotten more clarity out of the situation with my internist today. From his perspective he believes that i have had a couple of episodes of delusional thinking that is caused by interferon. He is contacting my liver doc today to see if it will be possible to discontinue IFN. He says he has seen this in Hep C treating patients before and that it overwhelmingly reverses post tx. however he has seen a few cases where it persisted. So we will see what the two of them figure out, but he doesn’t believe it is a depression based on what i have described to him.
have you heard of that before?
Deb
Deb–
I’m not sure I get the severity of the symptoms that you experienced. Unless there is more to it, what you describe is not delusion but self doubt. Do YOU think it reached delusional proportions????? I would hate for you to limit your otherwise successful and well tolerated IFN treatment because of a bad week. Let me know.
–DH MD
Dr. Dan,
My DR. put me on Seroquel (300) at night and Effexor XR 75 twice a day. It worked well i felt better completely, however I got pain where my liver soon after I started to feel better. So again I got scared and just stopped taking them and went to see him but he does not think they would cause that. I believe him, my liver biopsy was stage 1 grade 1, so i know i have a somewhat good liver. But All i do all day is think about the pain, worry about it and get depressed and do not want to do anything because I think I am going to die. And I do not want to think this way. I try everyday to keep a good attitude but its hard. What can I do? I have a great doctor, but I get the pain and then I stop taking the meds and I am back to square 1. Any advice would help, I have read so much I do not know what to believe about this meds, but all i know is it helped some. Thanks for your time.
Matt– It was a little unclear about the sequence of events. Sounds like you had no pain, went on the meds and got pain, went off meds, pain went away, had biopsy, now sit and worry. My question would be . . . what would happen if you went back on the medicine? Would the pain return? If it did, what would cause that?? That, of course, would be a question for the GI specialist and not the shrink. If you have already done that (ie went back on the meds and got pain again), I would suggest a trial of new medicine to treat your symptoms.
Problem with first-time “side-effects” is that there are many potential causative factors for all sorts of “side-effects”. If you wait long enough (and that time period can be variable) the situation can resolve on its own. Now with your situation, you don’t mess with your liver . . . so make sure that the GI guy is in the loop as these decisions are made. If the pain only occurred once, it would not be unreasonable to try again. If the pain occurred on re-challenge. Use something different.
–DH MD