Is fluoxetine (selective serotonin reuptake inhibitor) addictive?

Is Fluoxetine Addictive?

Fluoxetine (Prozac) is not addictive in the traditional sense, though it can cause discontinuation symptoms if stopped abruptly, particularly at higher doses or after long-term use.

Understanding Fluoxetine's Pharmacology

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that works by inhibiting the reuptake of serotonin in the brain. Unlike substances with high addiction potential, fluoxetine:

• Does not produce euphoria or a "high"
• Is not associated with drug-seeking behavior
• Does not lead to tolerance requiring escalating doses for the same effect
• Is not classified as a controlled substance

Discontinuation Symptoms vs. Addiction

While fluoxetine is not addictive, it can cause discontinuation symptoms when stopped abruptly:

• Fluoxetine has a long half-life (1-3 days for the parent compound and up to 7 days for its active metabolite norfluoxetine after long-term use) 1
• This long half-life provides a natural tapering effect, making discontinuation symptoms less common than with other SSRIs 2
• When discontinuation symptoms do occur, they may include dizziness, lightheadedness, nausea, and headache 2

In rare cases, more severe reactions can occur:

• A case report documented delirium following abrupt discontinuation of fluoxetine, though this is considered unusual 3

Clinical Evidence on Discontinuation

A randomized, placebo-controlled study specifically examining fluoxetine discontinuation found:

• After 12 weeks of treatment (20 mg/day), patients abruptly switched to placebo showed similar rates of new or worsened adverse events compared to those continuing fluoxetine
• Only mild, self-limited lightheadedness or dizziness occurred in a small percentage of patients
• No cluster of symptoms suggestive of a discontinuation syndrome was observed
• Researchers concluded that "abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk" 2

Comparison to Other Antidepressants

Fluoxetine has a more favorable discontinuation profile compared to other antidepressants:

• Withdrawal symptoms are common with paroxetine, venlafaxine, and fluvoxamine
• Discontinuation symptoms are relatively rare and mild with fluoxetine cessation due to its longer half-life 3
• Guidelines note that "fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and/or discontinuation" 2

Clinical Recommendations

When prescribing or discontinuing fluoxetine:

1. Inform patients that fluoxetine is not addictive but may cause discontinuation symptoms if stopped suddenly
2. For most patients on standard doses (20 mg/day), abrupt discontinuation appears well-tolerated 2
3. For patients on higher doses or with longer treatment duration, consider a gradual taper
4. Monitor for uncommon but possible discontinuation symptoms including dizziness, headache, and nausea

Special Considerations

• Duration of therapy for depression typically requires at least four months of treatment after remission of symptoms 4
• Patients with recurrent depression may benefit from prolonged treatment 4
• When discontinuing antidepressants, a gradual reduction over 10-14 days can limit withdrawal symptoms 4

In conclusion, while fluoxetine requires proper medical supervision for both initiation and discontinuation, it does not possess the addictive properties associated with substances of abuse.