Question

Which of the following would be your next step?

Do nothing as his SSRI is starting to become effective after three weeks of use

His side effects are strange but minor; convince him to tolerate his medication longer

Increase the SSRI for better effect

Change to an alternate SSRI in the hope of continuing this early efficacy but without the paresthesia

Change classes to a different family of antidepressant

Add an anti-paresthesia medication such as gabapentin (Neurontin)

Refer for specific IPT, which is well studied for depression when caused by interpersonal role change such as a loss of work

Attending physician’s mental notes: initial evaluation (continued)

The patient is somewhat better after three weeks of SSRI treatment, but this equates to 20% better at most, as only two MDD symptoms are minimally better

If patient can tolerate his side effect a bit more and given this initial small response, it may make sense to increase his current SSRI, sertraline (Zoloft) further

Further investigation

Is there anything else you would especially like to know about this patient?

Could there be any other cause to the strange sensations in his hands?

• – Physical examination reveals no clear skin changes or deformities

• – He has full range of motion, no arthritic changes

• – He has no history of cervical injury or pain

• – None of the medications are known to cause this kind of side effect

• – There is no evidence of carpal tunnel or other entrapment syndrome

• – Discussions with his PCP confirms these findings

• – He has leg pain and neuropathy from his diabetes, it is possible that these hand pressure sensations are the start of diabetic neuropathy in his upper extremities that presented coincidentally with the start of his SSRI

Case outcome: first interim follow-up visits through three months

Agrees now to increase the SSRI sertraline (Zoloft) to 100 mg/d and to tolerate the side effect of greasy hands as it is explained that it may be a rare side effect or part of his DM2

Later feels better but qualifies this as being less ruminative, less tense, and sleeping better, but still often feels amotivated and dysphoric

The SSRI dose is raised to 150 mg/d and he returns with moderate, sustained improvement in these symptoms and he feels his appetite is better

Question

Do the SSRIs have a dose–response curve where greater doses treat a greater number of symptoms?

No, according to regulatory information, there is no additional benefit between low, moderate, and high doses of SSRI when used to treat MDD

No, studies suggest that low doses of SSRI successfully inhibit the SERT, indicating that further inhibition is likely not needed for greater antidepressant response

Yes, in clinical practice, many clinicians claim that higher doses usually aid in more symptom reduction

Yes, textbooks and a recret meta-analysis suggest higher dosing on an individual basis to deliver the highest effectiveness

Possibly, as regulatory trials often contain 300–400 subjects and are statistically designed to show that all doses are superior to placebo but not necessarily to each other

• – They are not designed with enough subjects, i.e., 1500 or enough statistical power to show discrete differences between low, middle, and higher doses