Cases That Test Your Skills

Agitated and depressed with a traumatic brain injury

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Valproic acid stands out among anticonvulsants because its superior antioxidant effects, in combination with its antiepileptic effect in patients with TBI, offer more neuro­protection than other medications.5 It is important to regularly monitor ammonia levels in patients receiving valproic acid because elevated levels can cause hyperammonemic encephalopathy.

A 2005 study by DeBattista et al5 investigated the impact of valproic acid on agitation in 12 adults with MDD who were being treated with antidepressants. Participants were given a low dose of valproic acid for 4 weeks and their agitation, anxiety, and depressed mood were independently assessed by separate rating scales. There was a modest decrease in scores for mood symptoms but a particularly sharp decrease in agitation scores.5

Valproic acid has been shown to be a potentially safe and efficacious treatment for alcohol withdrawal. A clinical trial examining patients with moderate alcohol withdrawal found a faster and more consistent resolution of symptoms in patients given valproic acid detoxification compared to a control group that received the standard benzodiazepine detoxification.6 Additionally, patients who continued maintenance valproic acid following detoxification were completely abstinent at 6-week follow-up compared to patients who did not receive this maintenance therapy.6

Valproic acid was a particularly optimal medication choice for Mr. N due to its neuroprotective properties in the context of TBI, its ability to treat delirium,7 its lack of abuse potential compared with benzodiazepines, and its potential efficacy for managing alcohol withdrawal and AUD.

OUTCOME Improvement and discharge

Mr. N is medically cleared for discharge. Although the psychiatry team initially was concerned about his willingness to attend follow-up appointments and adhere to proper cervical collar use, Mr. N becomes more cooperative with psychiatric care as his stay continues, and he is psychiatrically cleared for discharge 1 month after admission. Discharge plans include attending an intensive outpatient program, continuing the inpatient psychiatric medication regimen, participating in regular outpatient psychiatric follow-up, as well as following up with orthopedic surgery, neurosurgery, podiatry, and ear, nose, and throat for medical conditions.

Bottom Line

Agitated depression is a mixed state that includes features of depression and manic/hypomanic symptoms. Diagnosis and treatment can be challenging because symptoms of agitated depression overlap with bipolar disorder and antidepressants are contraindicated. In a patient with a traumatic brain injury, pharmacotherapy that provides neuroprotection is a priority.

Related Resources

  • Ramaswamy S, Driscoll D, Rodriguez A, et al. Nutraceuticals for traumatic brain injury: should you recommend their use? Current Psychiatry. 2017;16(7):34-38,40,41-45.
  • Sampogna G, Del Vecchio V, Giallonardo V, et al. Diagnosis, clinical features, and therapeutic implications of agitated depression. Psychiatr Clin North Am. 2020;43(1):47-57. doi: 10.1016/j.psc.2019.10.011

Drug Brand Names

Amantadine • Gocovri
Aripiprazole • Abilify
Asenapine • Saphris
Brexpiprazole • Rexulti
Buspirone • BuSpar
Carbamazepine • Tegretol
Cariprazine • Vraylar
Clozapine • Clozaril
Dexmedetomidine • Igalmi
Diazepam • Valium
Donepezil • Aricept
Gabapentin • Neurontin
Haloperidol • Haldol
Ketamine • Ketalar
Lacosamide • Vimpat
Lamotrigine • Lamictal
Levetiracetam • Keppra
Lithium • Lithobid
Lorazepam • Ativan
Lurasidone • Latuda
Memantine • Namenda
Methylphenidate • Concerta
Mirtazapine • Remeron
Olanzapine • Zyprexa
Oxcarbazepine • Trileptal
Paliperidone • Invega
Phenytoin • Dilantin
Pramipexole • Mirapex
Pregabalin • Lyrica
Quetiapine • Seroquel
Risperidone • Risperdal
Trazodone • Oleptro
Valproic acid • Depakene
Ziprasidone • Geodon
Zolpidem • Ambien
Zonisamide • Zonegran


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