Quetiapine for ADHD

Quetiapine is an atypical antipsychotic.¹
It also has an antidepressant effect.²
Quetiapine has addictive potential and is increasingly being abused.³

In lower doses, it is used as a sleeping pill. The relatively short plasma half-life of 2.5 to 5 hours⁴ is favorable for this.

• 1. Effect of quetiapine
  • 1.1. Quetiapine acts as an antagonist
  • 1.2. Quetiapine acts as an agonist
• 2. Use of quetiapine

1. Effect of quetiapine¶

1.1. Quetiapine acts as an antagonist¶

Quetiapine acts as an antagonist:

• Serotonin receptor 5-HT2A²
  • Thereby increasing the dopamine level in the PFC
• Serotonin receptor 5-HT2C via the metabolite norquetiapine²
  • Receptor binding in the PFC of 72 % after 2 hours at 450 mg⁴
  • Receptor binding of 50 % after 26 hours at 450 mg⁴
• Dopamine receptor D2
  • Leads to antipsychotic effect
  • Receptor binding in the striatum of 44 % after 2 hours at 450 mg⁴
  • Receptor binding after 26 hours as in untreated healthy individuals at 450 mg⁴
  • The D2 antagonism of quetiapine is therefore weaker than the 5HT antagonism.⁵
  • Relatively low affinity for dopamine D2 receptors, with an occupancy half-life of 10 hours, which was around twice as long as that of plasma⁴
• Σ-Adrenoceptor (especially A2)²
  • Thereby increasing the dopamine level in the PFC
• Noradrenaline transporter NAT via the metabolite norquetiapine²
  • Resulting in increased noradrenaline levels
• Histamine receptor H1
• Glutamate NMDA
  • Quetiapine reduces the mRNA levels for some subunits of the glutamate NMDA receptor NR-1 and NR-2.²
  • Reduction in the density of NMDA receptors in the caudate nucleus (putamen) (but not in the cortex or limbic system), as well as clozapine or haloperidol²

1.2. Quetiapine acts as an agonist¶

Quetiapine acts as an agonist:

• Serotonin receptor 5-HT1A (partial)²
  • Thereby increasing the dopamine level in the PFC
• Glutamate-AMPA
  • Increase in the density of glutamate AMPA receptors in the caudate nucleus (putamen) (but not in the cortex or limbic system), as well as clozapine or haloperidol ²
  • Quetiapine caused a significant increase in the GluR-B and GluR-C subunits of the AMPA receptor in the hippocampus of rats.²
• Sigma-1 receptors
  • Conveys antidepressant effect⁶
    • Can be additionally increased by σ1-agonists (+)-pentazocine
    • Can be reduced by σ1 antagonists BD1063

The indirect inhibition of the 5-HT2C receptors causes an inhibition of GABA release in the brain stem, which in turn causes a release of noradrenaline and dopamine in the PFC.²

According to this understanding, GABA is underrepresented in ADHD-I and overrepresented in ADHD-HI. Against this background, quetiapine would hypothetically be more useful in ADHD-HI and less recommended in ADHD-I,

2. Use of quetiapine¶

Quetiapine is mainly used for schizophrenia or bipolar disorder (manic-depressive).
In the case of ADHD, use has so far tended to be in relation to (massive) comorbidities rather than ADHD itself.

A study on the treatment of ODD by administering quetiapine (= augmentation) in addition to an SSRI did not find any significant improvement in the effect.⁷

In ADHD, quetiapine is used off-label in low doses for the frequent sleep problems. Due to its short half-life, it can be used for this purpose despite the (albeit relatively weak) D2 antagonism.⁸ Nevertheless, quetiapine at 450 mg showed a receptor occupancy of the dopamine D2 receptors in the striatum of 44 % within 2 hours, which only fell back to the level of untreated healthy volunteers after 26 hours.⁴ As a sleeping pill, however, quetiapine is dosed at between 12.5 and 100 mg, much lower than in schizophrenia or bipolar disorder.
In view of the potential for addiction and abuse of quetiapine, it should be used with great caution.³