The initial published case has been modified slightly in response to feedback from colleagues.
We return to Juan, the 20 yo man from our last PsychSnap. He started hearing the voice of a little boy saying things like “why won’t you help me” three months ago. He now hears the voice multiple times a day, which he finds very distressing. He thinks his neighbor kidnapped a boy and created an electric field that prevents other people from hearing the boy crying for help. Because Juan was implanted with a chip in his brain by the government, he alone can hear the boy’s cries. Juan has become more socially withdrawn over the last 6 months and stopped attending his college classes one week ago.
In Part 1, we discussed how to talk with Juan about his experience of hearing voices and screen for other symptoms of psychosis. In this PsychSnap, we will discuss the medical work-up and initiation of treatment for the first episode of psychosis in a young person.
Medical Workup – The differential diagnosis for psychosis is broad, but the essential medical work-up for a healthy young person is straightforward. The review of systems, physical exam, and labs evaluate for “non-psychiatric” causes of psychosis. Your suspicion for these should increase if the patient has experienced:
- Sudden onset of psychosis (hours to days), as compared to the subacute onset typical of both schizophrenia-spectrum disorders and mood disorders with psychotic features
- Visual hallucinations without associated auditory hallucinations
- Disorientation or confusion
- Focal neurologic signs or symptoms, including seizures
Pertinent “Non-Psychiatric” Review of Systems
- Drug use – in particular cannabis & stimulant use
- Neuro – loss of consciousness, seizures, changes in vision, new headaches, numbness or weakness
- Rheum/Endocrine – pain, rashes, joint swelling, oral ulcers, fatigue, hot or cold intolerance
- Recent illness or travel
Exam – Basic physical exam, paying particular attention to the neuro, rheum, and endocrine systems.
- CBC w diff for baseline white and red blood cell counts
- CMP for electrolyte abnormalities, particularly in sodium and calcium which could be signs of Addison’s disease or hyperparathyroidism. Liver function tests as a baseline. Abnormal LFTs would also raise the suspicion for Wilson’s disease.
- Comprehensive urine drug screen, likely the lab test with the highest yield
- TSH for hyper or hypothyroidism
- Vitamin B12 +/- methylmalonic acid for Vitamin B12 deficiency
- Folate for prevention of schizophrenia. Although rare in the US, low levels of folate are associated with a higher risk of schizophrenia, and there is some evidence that supplementation of low folate levels may prevent the development of schizophrenia.
- FTA-Ab for neurosyphilis. The RPR titer declines over time and can occasionally become negative in tertiary syphilis.
- HgA1c and cholesterol panel to establish a baseline if you are starting an antipsychotic medication.
Many sources also recommend laboratory screening with ANA for lupus psychosis and ceruloplasmin for Wilson’s disease. Both labs make poor screening tests. I recommend ordering an ANA if the rheum ROS is positive, and a ceruloplasmin level (and ocular exam) if the psychosis is associated with a movement disorder or unexplained liver abnormalities.
Imaging – You do NOT need to get head imaging if there are no focal neuro signs in a young adult with first episode psychosis (Skikic, 2020). If you don’t have time for a complete neuro exam in the initial visit, you can do it during the second visit.
Juan has been hearing a voice for three months that is now connected with an elaborate delusional explanation that is causing significant distress and a major functional impact. If someone is unlikely to connect with psychiatry soon, consider starting an antipsychotic medication for persistent auditory hallucinations connected to a delusional explanation that are interfering with functioning. If auditory hallucinations are infrequent or non-distressing without a delusional belief system, it is reasonable to monitor the patient until they can connect with a psychiatrist.
There are >25 antipsychotic medications available, but you can get started with the vast majority of patients with first episode psychosis by knowing how to use three medications: aripiprazole, lurasidone, and olanzapine.* All are highly effective, accessible second generation antipsychotic medications. Most of the risks associated with antipsychotic medications are with long-term exposure.
The initial response to an antipsychotic begins within 1–2 weeks, with a significant response expected within 2–4 weeks. My hope for an antipsychotic medication trial is that Juan takes a medication and the voice becomes softer, less frequent, and less distressing to him so that he can re-engage with his college courses. I also hope that it will “soften” his delusion — making him less sure about his belief that his neighbor kidnapped a boy. We can use the percentage (%) of the day that Juan hears voices as one marker of the severity of auditory hallucinations, and as a measure of therapeutic response that we can follow over time.
I generally start with aripiprazole 2.5mg (1/2 of 5mg pill) in the morning and increase to 5mg after a week. If there is no response to aripiprazole 5mg after 2-3 weeks, increase the dose to 10mg. Stop the titration if you have some response (the full response will take about a month at a given dose), side effects limit further titration, or you’ve reach the top of the target dose (see the table below) without a response.
Aripiprazole is reasonably well-tolerated, with a lower risk of sedation than many antipsychotics, and a low-to-moderate risk of weight gain and metabolic side effects. It is also available in a long-acting injectable form. The two most common side effects of aripiprazole are weight gain and akathisia, a distressing feeling of restlessness that is an extrapyramidal side effect of antipsychotic medications. Akathisia generally starts within a few days to weeks of starting an antipsychotic medication or increasing the dose. If a patient develops akathisia, reduce the dose as much as possible (for aripiprazole, go down to 1mg). If the akathisia resolves, you can try titrating the medication more slowly. If the akathisia recurs, switch to another medication.
|Starting & Target Daily Dose
|Other Side Effects & Clinical Pearls
|5mg daily (qam)
(2.5mg for the first week, break 5mg pill in half)
Target: 5-15 mg
|moderate risk of akathisia
can cause insomnia
with 350 cal to increase absorption
Target: 20-60 mg
|moderate risk of EPS (dystonia, akathisia, parkinsonism)
sedating and can help with sleep
and therefore not recommended as first line treatment in young people
|very effective antipsychotic & generally well-tolerated in the short term.
sedating and can help with sleep
Lurasidone (Latuda) is an effective antipsychotic medication that can be used if sedation is a desired side effect, or if aripiprazole is ineffective or intolerable. Lurasidone (Latuda) became a generic medication in 2023. Lurasidone stands out among the antipsychotic medications for its low risk of weight gain and metabolic problems. It has a moderate rate of extrapyramidal side effects, including dystonia, akathisia, and parkinsonism. Latuda’s absorption is also cut in half if taken without food.
Olanzapine is not recommended as a first line treatment for psychosis in young people due to its high long-term metabolic risk. However, if the patient is highly skeptical of medications, due in part to their psychosis, I may start with olanzapine if it seems like I’ll only get one-shot at treatment. Olanzapine is generally well-tolerated when it is started. When the patient’s symptoms are better controlled, I would plan to transition from olanzapine to aripiprazole.
How can we help Juan?
You discuss the plan with Juan and his mother together. You highlight that Juan has shared some distressing experiences with you, including hearing voices. You are glad that they came in to see you. This is nobody’s fault, and you expect that Juan’s symptoms will improve. You encourage Juan to continue to avoid cannabis and stimulants, as these can make psychotic experiences worse. Because the review of systems and physical exam focused on the neuro, endocrine, and rheum systems were negative, the only workup recommended at this time are the labs: CBC w diff, CMP, comprehensive urine drug screen, TSH, Vitamin B12 +/- methylmalonic acid, folate, HIV, and FTA-Ab, cholesterol panel, and HgA1c. No head imaging is recommended.
You recommend that he start medication to quiet the voice and help induce doubt about whether his neighbor kidnapped a boy. You prescribe aripiprazole 5mg daily, start with ½ pill in the morning for 1 week, then 1 full pill daily. If he finds that the medication makes him sleepy, he can switch it to bedtime. You let him know to call if he becomes restless or has any other side effects from the medication.
You would like to refer him to a clinic that specializes in working with people who have similar experiences. You arrange a follow-up appointment with you in two weeks and refer him to the Early Psychosis Coordinated Specialty Care Program at your local university.
Early Psychosis Coordinated Specialty Care Programs provide multidisciplinary care to young people experiencing psychosis for the first time. They should be specifically sought out if they are available in your area. They commonly offer individual therapy (CBT for psychosis), family psychoeducation, group therapy and psychiatric care with medications. There is a National Early Psychosis Directory that locates the closest programs https://easacommunity.org/national-directory.php or you can use this interactive map that uses the same data but is easier to navigate. https://med.stanford.edu/peppnet/interactivedirectory.html. If the program contact does not respond, search for the program online, as staff turnover can make the specific staff contact out of date.
*Aripiprazole, lurasidone, and olanzapine are also highly effective medications in treating mood disorders in people who do not experience psychosis. Aripiprazole is the most well-studied augmentation agent for unipolar depression, lurasidone is FDA approved for bipolar depression, and olanzapine is a potent anti-manic agent. The starting doses for all three medications in mood disorders are the same as for first episode psychosis. All three antipsychotics can also be helpful in treating chronic psychosis. The maintenance doses in chronic psychosis tend to be higher than for first episode psychosis.
- Schizophrenia spectrum disorders or mood disorders with psychotic features usually present sub-acutely over weeks to months, and do not include disorientation, focal neurologic signs, or visual hallucinations without auditory hallucinations.
- An appropriate medical work-up for a young person experiencing psychosis for the first time includes a history of drug use, review of symptoms and physical exam focused on the neuro, rheum, and endocrine systems, and labs (CBC w diff, CMP, comprehensive urine drug screen, TSH, Vitamin B12 +/- methylmalonic acid, folate, HIV, and FTA-Ab, cholesterol panel, and HgA1c).
- If auditory hallucinations are distressing, persistent, frequent, and associated with a delusional belief system, consider starting treatment with an antipsychotic medication.
- If starting an antipsychotic medication for first episode psychosis, go with low-dose aripiprazole. If a patient is guarded or suspicious and you worry about getting only “one shot” with a medication, consider starting with olanzapine with the goal of short-term stabilization.
Thank you to Dr. Demian Rose, Professor of Psychiatry at UCSF, for his careful review of this PsychSnap.
Skikic, Maja, and Jose Alberto Arriola. “First episode psychosis medical workup: evidence-informed recommendations and introduction to a clinically guided approach.” Child and Adolescent Psychiatric Clinics 29.1 (2020): 15-28.
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