Irritability during antidepressant trials

What does it mean when someone has a negative reaction to antidepressants?  Most people put on antidepressants do well.  They have minimal to no side effects and have a gradual improvement in their mood/anxiety.  For some people, a trial of an antidepressant is a nightmare.  Any time an antidepressant is initiated, you can experience irritability, aggression, a paradoxical increase in sadness, and even (in rare cases) a serious increase in suicidal ideation.

What does it mean?

Obviously the ultimate meaning of a bad reaction must be evaluated in the context of the complicated clinical and psychosocial picture of the individual with the reaction.  It must not, however, be ignored.  Here are several circumstances and a brief interpretation of what it could mean.  Remember, these is just a brief overview–make sure you talk to your doctor:

MORE DEPRESSED:  Suppose you get more depressed on an antidepressant.  By that, I mean a nearly immediate drop in your mood when a medicine is started.  It may be a worsening of the existing symptoms (eg, more fatigued, worse concentration, more difficulty enjoying yourself).  It may also present as a dramatic emergence of symptoms that were not previously an issue.  This is different than a continued gradual progression in the pattern of mood symptoms which would indicate a lack of effectiveness in the medicine rather than a negative reaction.  If there is a dramatic worsening of symptoms, I typically stop the medicine and watch how things progress and change over the course of a few days or a few weeks.  What I look for when someone is having this type of reaction on antidepressants is for his or her mood to return to the ‘regular’ amount of depression that was being experineced before the medicine was started.  Once we get back to that baseline, I will try another antidepressant.  Is there deep meaning behind this type of reaction.  Typically not.  This type of reaction to a medicine has little to no predicitive value for how someone will react to other medicines.  If someone has a similar reaction to a similar medicine, that starts having predicitve value.  For example, if both Celexa and Zoloft cause this type of reaction, I would be more reluctant to initiate a trial of another SSRI, and would choose a medicine with a different mechanism of action.

SUICIDAL:  Worrysome . . . very worrysome.  This type of reaction to an antidepressant is also very ideosyncratic and unpredictable.  It also has no predicitve value, unless it occurrs again with a medicine that is similar in action (eg two SSRI’s).  Anytime someone has enhanced suicidal ideation in responce to a medicine, it is time to step back and reinforce the psychosocial supports available to the patient.  It is important that he or she understand the ‘side-effect’ nature of the suicidality and how to manage it should it reoccur.  Specific management strategies need to be in place, especially designated ‘rescue’ people–people who know that the patient is on medicine and understand the reaction that did occur and could occur with the next trial.  Should an increase in suicidal thoughts occur, the medicine should be stopped and the patient carefully monitored until the pattern of thoughts decreases to the previous level.  Having suicidal thoughts on one antidepressant does not mean that you will get suicidal thoughts on another antidepressant.

IRRITABILITY:  This is an interesting reaction because it can have meaning . . . BIG meaning.  Profound irritability on antidepressants can indicate the possibility of an underlying or emerging Bipolar Disorder.  In patients who have a family history of Bipolar Disorder, it has greater predictive value.  It has even greater predictive value in patients who experience an irritable reaction to two or more antidepressants, regardless of the class of the antidepressants.  Does irritability mean that you have Bipolar Disorder.  No.  Only when the irritability is associated with other symptoms that are typical of Bipolar Disorder–eg hyper-talkativeness, decreased need for sleep, dangerous impulsive behavior, etc.  Regardless of the presence of other Bipolar symptoms, if someone becomes very irritable on more than one antidepressant, it signals to me the need to start a mood stabilizer before initiating another antidepressant trial.  Low or moderate doses of Depakote is usually my recommendation.

–Dan Hartman, MD

2 comments to Irritability during antidepressant trials

  • louise

    I read the above post from aug 2cnd on irritability on antidepresants. However, what if someone actually has depression with irritability and the irritability is markedly improved on ssris,however, after time, the depresion symptoms return ?

  • A couple of issues come to mind with this. Was there irritability prior to the depression? Was the irritability only with the depression but the depression was a long term issue (like a dysthymia that got way worse)? Regardless, what you describe is not an uncommon scenerio. There is many ways to address this (you didn’t give details on meds so I will just spout advice here in a more random fashion). As always, I would encourage those mood supportive techniques that I have mentioned elsewhere–therapy, vitamines, fish oil, etc. If the ssri is not at the max dose, it would be reasonable to go up on the dose of the medicine. It would also be reasonable (if you are at the max dose) to try another ssri OR to add in wellbutrin to the ssri to get coverage of the depression symptoms while trying to hold control over the irritability. No right or wrong answer here–just lots of options for you (that is a good thing). Let me know how things are.
    –DH MD