References

1. Stahl SM, Antidepressants, in Stahl’s Essential Psychopharmacology, 3rd edition, Cambridge University Press, New York, 2008, pp 511–6662. Stahl SM, Disorders of Sleep and Wakefulness and their Treatment, in Stahl’s Essential Psychopharmacology, Cambridge University Press, New York, 2008, pp 815–8623. Stahl SM, Aripiprazole, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 45–504. Stahl SM, Quetiapine, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 459–645. Stahl SM, Gabapentin, in Stahl’s Essential Psychopharmacology The Prescriber’s Guide, 3rd edition, Cambridge University Press, New York, 2009, pp 221–2256. Silberstein S, Marmura M, Stahl SM (Ed), Pramipexole, in Neuropharmacology: The Prescriber’s Guide, Cambridge University Press 2010, pp 262–2657. Stahl SM, Diagnosis and Treatment of Sleep Wake Disorders, NEI Press, Carlsbad, California, 20078. Stahl SM, Sleep: Excessive Sleepiness, NEI Press, Carlsbad, California, 20059. Marangell LB, Martinez M, Jurdi RA et al. Neurostimulation Therapies. Acta Psychiatrica Scandinavica 2007; 116: 174–18110. Bassetti C, Gugger M, Bischof M et al. The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexinA). Sleep Medicine 2003; 4: 7–12

Patient FileLightning RoundThe Case: The woman who felt numb

The Question: Are the complaints of a 63-year-old woman with a complex set of psychiatric conditions due to incomplete recovery, or to SSRI induced apathy?

The Dilemma: How to have your cake and eat it, too: namely, remission from psychiatric disorders yet no drug-induced cognitive side effects

Pretest Self Assessment Question(answer at the end of the case) Which of the following is theoretically false regarding apathy?

A. It can be a residual symptom of depression

B. It can be a side effect of serotonergic antidepressants

C. It is hypothetically due to elevated dopamine

D. It is hypothetically due to elevated serotonin decreasing dopamine

Patient Intake 63-year-old woman

Chief complaint “feeling numb”

Psychiatric History Long history since teens of affective, substance abuse and eating disorders

Depressive episodes since teens

Alcoholic starting in teens, but sober now for 27 years

Three suicide attempts, two in her 30s, one in her 40s, overdoses, related to relationship issues when she married and divorced the same man twice

Restricting anorexia with laxative abuse since teens, with weight as low as 89 pounds as recently as 16 years ago, responsive to inpatient treatment and fluoxetine (Prozac) 60 mg

Stormy relationship with her mother

Father with history of depression

Has developed progressive sense of becoming “numb” over the past 10 years, meaning apathy, loss of memory and problems concentrating

Numb feelings attributed to fluoxetine, but every time she has stopped it over the past years, began to have “rages” and “panic”

Currently taking fluoxetine 60 mg because taking it is not as bad as stopping it

Of the following choices, what would you do?

Switch to another SSRI

Switch to an SNRI

Switch to mirtazapine (Remeron)

Switch to bupropion (Wellbutrin)

Initiate or refer to psychotherapy

Case Outcome Patient switched to bupropion, but developed “rage” and also anxiety while driving

Switched to lamotrigine (Lamictal), and has done well for many months without recurrent depression, rage, or apathy

Case Debrief It appears as though this patient’s complaints of numbness were indeed due to her fluoxetine treatment

Despite her unstable past, she has done well from a psychiatric point of view in recent years except for her apathy and problems concentrating since taking fluoxetine

She destabilizes when stopping fluoxetine, so some alternative treatment is necessary

Switching to another SSRI seems very unlikely to be helpful, as would switching to an SNRI, since the apathy is theoretically due to raising of serotonin levels, which can reduce dopamine release in some brain circuits, especially in patients who are very sensitive to this for unknown reasons

Mirtazapine also raises serotonin

Bupropion is the most logical choice because it does not raise serotonin, and in fact raises dopamine (and norepinephrine) and even reverses SSRI apathy in patients who are switched to bupropion or who are augmented with bupropion

This patient may have a contraindication to bupropion in the opinion of some psychopharmacologists because of the remote history of eating disorder; however, this problem is not active, and the patient is at normal body weight, so bupropion can be given safely and prudently

Surprisingly, bupropion did not work

Another agent that lacks serotonergic properties is lamotrigine, which may act via blockade of glutamate release

This patient surprisingly responded well to this switch, possibly because the patient has a bipolar spectrum disorder as part of her complex psychiatric problems, and thus is responsive to an agent better known for preventing recurrences of depression in bipolar patients

Posttest Self Assessment Question: Answer Which of the following is theoretically false regarding apathy?

A. It can be a residual symptom of depression

B. It can be a side effect of serotonergic antidepressants

C. It is hypothetically due to elevated dopamine

D. It is hypothetically due to elevated serotonin decreasing dopamine

Answer: C