Medications for Long-Term Treatment of Depression, Anxiety, and Related Disorders*

Medications for Long-Term Treatment of Depression, Anxiety, and Related Disorders*
Medication	Uses	Half-life (hrs)	CYP substrates	Comments/Precautions
SSRIs
CitalopramCitalopram	OCD in children ≥ 7 years	35 hrs	2C19, 2D6	For 2C19 poor metabolizers, lower starting dose, slower titration and 50% reduction of maintenance dose
Escitalopram (S-enantiomer of citalopram)Escitalopram (S-enantiomer of citalopram)	Major depression in children ≥ 12 years	27–32 hrs	2C19, 2D6	—
Fluoxetine†Fluoxetine† Norfluoxetine (active metabolite of fluoxetine)Norfluoxetine (active metabolite of fluoxetine)	OCD, GAD, separation anxiety, social anxiety, major depression in children > 8 years	119–264 hrs Norfluoxetine: 144–384 hrs	2D6	—
FluvoxamineFluvoxamine	GAD, separation anxiety, social anxiety, OCD in children > 8 years	16 hrs	2D6	—
Paroxetine†Paroxetine†	OCD in children > 6 years	21 hrs	2D6	—
SertralineSertraline	OCD, GAD, separation anxiety, social anxiety in children ≥ 6 years	26 hrs	2C19, 2B6, 2D6	For 2B6 poor metabolizers, lower starting dose, slower titration and 25% reduction of maintenance dose
SNRIs
DuloxetineDuloxetine	GAD in children 7–17 years	10–12 hrs	2D6, IA2	SNRIs: have noradrenergic activity and can increase risk of hypertension
Venlafaxine, immediate-releaseVenlafaxine, immediate-release	Depression in children ≥ 8 years	5–11 hrs	2D6	SNRIs: limited data about optimal dose; concerns about increased suicidal behavior (in adolescents with pre-existing suicidal ideation); not as effective as other antidepressants, possibly because low doses have been used
Venlafaxine, extended-releaseVenlafaxine, extended-release	GAD in children > 7 years	—	—
* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram.* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram.
† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses.† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses. Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression. Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression. Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue). Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue).
CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor.CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor.

* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram.* The medications listed are used clinically for all the anxiety disorders, OCD, and depression. FDA approval has been obtained for some conditions; the lack of FDA approval for other conditions is due to a lack of sufficient studies and not due to other reasons. The most commonly used across all conditions are sertraline and escitalopram.

† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses.† Fluoxetine and paroxetine are potent inhibitors of 2D6, decreasing the metabolism of antipsychotics (risperidone, aripiprazole, iloperidone, clozapine), increasing their plasma concentration. They can also inhibit the metabolism of some pain medications to their active metabolite (oxycodone to oxymorphone) but contrary to expectations, not codeine to morphine. Less potent inhibitors of 2D6 (sertraline) may have similar effects at the higher doses.

Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression. Fluoxetine and paroxetine efficacy in treating depression is compromised when combined with trazodone (used to treat insomnia). This is attributed to 2D6 interactions and accumulation of methyl-chloro-piperazine a, trazodone metabolite associated with irritability and depression.

Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue). Cannabis or cannabidiol (CBD) and tetrahydrocannabinol (THC) are moderate to strong inhibitors of CYP enzymes, increasing SSRI plasma concentrations and contributing to adverse effects (eg, diarrhea, dizziness, fatigue).

CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor.CYP = cytochrome P450; FDA = Food and Drug Administration; GAD = generalized anxiety disorder; OCD = obsessive compulsive disorder; SNRI = serotonin-norepinephrine reuptake inhibitor; SSRI = serotonin reuptake inhibitor.

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