Question

How can you tell akathisia from mild serotonin syndrome?

Akathisia is either internal or external restlessness where the patient feels as though he or she needs to move incessantly, usually without other systemic side effects present

Mild serotonin syndrome, or toxicity, can have restlessness that is often attributed to anxiety and agitation

• – The symptoms are often described as a clinical triad of abnormalities

  • Cognitive effects: headache, agitation, hypomania, mental confusion, hallucinations, coma

  • Autonomic effects: shivering, sweating, hyperthermia, HTN, tachycardia, nausea, diarrhea

  • Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor

Attending physician’s mental notes: interim follow-up visits through six weeks

Patient is still depressed, suicidal with intrusive images

Failed an SSRI plus three separate atypical antipsychotic augmentations, all due to different side effects: akathisia, sedation, mild serotonin toxicity

Several weeks of high-dose SSRI has not improved symptoms

Outpatient personal and psychiatric support maximized in attempts to keep him safe and avoid a psychiatric hospitalization

Case outcome interim follow-up visits through 10 weeks

Lurasidone (Latuda) is discontinued and the mild serotonin toxicity resolves

As the differential diagnosis is still MDD with psychosis versus MDD plus OCD, or even mixed features, use of an atypical antipsychotic is still warranted

He is started on the fourth atypical antipsychotic, asenapine (Saphris)

• – Takes subtherapeutic 5 mg sublingual initially as this drug has a more sedating profile, which previously disturbed him while taking ziprasidone previously

• – This agent is known less for its akathisia and more for its sedating side effects

• – Metabolically, its trial data suggests minimal weight gain or metabolic problems over the long term, comparatively speaking

Trazodone (Desyrel) is discontinued and the asenapine (Saphris) increased to 10 mg sublingual, at bedtime to avoid oversedation in the mornings

• – Asenapine (Saphris) is usually dosed twice daily

• – In this case, as the patient is sensitive to sedation, it is felt better to leave all until bedtime to improve tolerability

• – Asenapine’s half-life is 24 h; thus, theoretically, it should allow for antipsychotic effects dosed once a day

• – It is the only atypical antipsychotic requiring sublingual dosing because the drug is not absorbed after swallowing whole as it cannot become activated

Tolerates escitalopram (Lexapro) 20 mg/d plus asenapine (Saphris) 10 mg/d and seems to appreciate getting to a combination that does not bother him or make him worse

• – He appears less despondent and more hopeful

Still is very depressed with intrusive images and asks for more aggressive medication options

• – Offered an escalation of the escitalopram SSRI to an off-label 30 mg/d as extra high doses of SSRI are warranted in some OCD patients

• – Offered a higher dose of the atypical antipsychotic asenapine again as a boost for his OCD, MDD, or as an antipsychotic in case his images are frank hallucinations

• Chooses to increase the SSRI to 30 mg/d