Treatment by comorbidity subtype
Treatment of psychosis generally begins with antipsychotics. Nominal psychotherapy (presence of a professionally detached, compassionate clinician) improves compliance and leads to supportive therapy. Cognitive-behavioral therapy and dialectical behavior therapy may help later, with limited interpersonal approaches further on for some patients.
The suggested approaches to pharmacotherapy noted here draw on research and clinical experience.1,14,19-21 All medications used to treat comorbidities noted here are approved or generally accepted for that diagnosis. Estimated doses are similar to those for comorbidities when patients are nonpsychotic, and vary among patients. Doses, dosing schedules, and titration are extremely important for full benefit. Always consider compliance issues, suicidality, possible adverse effects, and potential drug/drug interactions. Although the medications we suggest using to treat the comorbidities may appear to also benefit psychosis, only antipsychotics are approved for psychosis per se.
Delusional depression. Antipsychotic + antidepressant. Tricyclic antidepressants are possibly most effective, but increase the risk of overdose and dangerous falls among fragile patients. Electroconvulsive therapy is sometimes used.
Obsessive-compulsive schizophrenia. Antipsychotic + selective serotonin reuptake inhibitor (SSRI). Consider aripiprazole (consider long-acting injectable formulation for increased compliance). Aripiprazole also may enhance the benefit of fluoxetine for comorbid OCD. Carefully titrate, as tolerated, to optimal dose of fluoxetine (40 to 80 mg/d; the long half-life of fluoxetine and its metabolite norfluoxetine also improves compliance), while watching for activation and other adverse effects.21,22 Limited clinical experience suggests that lower-dose clonazepam every 12 hours may reduce the adverse effects of fluoxetine.
Schizophrenia with voices. Antipsychotic + clonazepam. Concurrent usage may stabilize psychosis more rapidly, and with a lower antipsychotic dose.23 Titrate a fixed dose of clonazepam every 12 hours (avoid as-needed doses), starting low (ie, 0.5 mg) to limit initial drowsiness (which typically diminishes in 3 to 10 days). Titrate to full voice and panic cessation (1 to 2.5 mg every 12 hours).14 Exercise caution about excessive drowsiness, as well as outpatient compliance and abuse. Besides alprazolam, other antipanic medications have little incidental benefit for psychosis.
Persecutory delusional disorder. Antipsychotic + SSRI. Aripiprazole (consider long-acting injectable for compliance) also enhances the benefits of fluoxetine for social anxiety. Long half-life fluoxetine (20 mg/d) improves compliance and near-term outcomes.
Bipolar I mania: mania with delusions. Consider olanzapine for acute phase, then add other antimanic medication (commonly lithium or valproic acid), check blood level, and then taper olanzapine some weeks later. Importantly, lamotrigine is not effective for bipolar I mania. Consider suicide risk, medical conditions, and outpatient compliance. Comorbid panic anxiety is also common in bipolar I mania, often presenting as nonthreatening voices.
Seasonality: Following research that bipolar I mania is more common in spring and summer, studies have shown beneficial clinical augmentation from dark therapy as provided by reduced light exposure, blue-blocking glasses, and exogenous melatonin (a darkness-signaling hormone).24
Bipolar I mania atypical depression (significant current or historical symptoms). SSRI + booster medication. An SSRI (ie, escitalopram, 10 mg/d) is best started several weeks after full bipolar I mania resolution, while also continuing long-term antimanic medication. Booster medications (ie, buspirone 15 mg every 12 hours; lithium 300 mg/d; or trazodone 50 mg every 12 hours) can enhance SSRI benefits. Meta-analysis suggests SSRIs may have limited risk of inducing bipolar I mania.25 Although not yet specifically tested for atypical depression, lamotrigine may be effective, and may be safer still.25 However, lamotrigine requires very gradual dose titration to prevent a potentially dangerous rash, including after periods of outpatient noncompliance.
Seasonality: Atypical depression is often worse in winter (seasonal affective disorder). Light therapy can produce some clinically helpful benefits year-round.
To illustrate this new approach to psychosis diagnosis and treatment, our book1 includes detailed case studies on each of the 5 psychosis subtypes. The brief fictional case we present in Box 2 describes a patient who had both premorbid social anxiety and panic anxiety, and then developed a mixed psychosis that reflected both of those contributing anxiety disorders.
Box 2
Social anxiety, panic anxiety, and mixed psychosis
Ms. B, a studious 19-year-old, has been very shy since childhood, with few friends. Meeting new people always gave her gradually increasing anxiety, thinking that she would embarrass herself in their eyes. She had that same anxiety, along with sweating and tachycardia, when she couldn’t avoid speaking in front of class. Sometimes, while walking down the street she would think that strangers were casting a disdainful eye on her, though she knew that wasn’t true. Another anxiety started when she was 16. While looking for paper in a small supply closet, she suddenly felt panicky. With a racing heart and short of breath, she desperately fled the closet. These episodes continued, sometimes for no apparent reason, and nearly always unnoticed by others.
At age 17, she began to believe that those strangers on the street were looking down on her with evil intent, and even following her around. She became afraid to walk around town. A few months later, she also started to hear angry and critical voices at sudden moments. Although the paroxysmal voices always coincided with her panicky symptoms, the threatening voices now felt more important to her than the panic itself. Nonpsychotic panics had stopped. Mostly a recluse, she saw less of her family, left her job, and stopped going to the movies.
After a family dinner, she was detached, scared, and quieter than usual. She sought help from her primary care physician, who referred her to a psychiatrist. A thorough history from Ms. B and her family revealed her disturbing fears, as well as her history of social anxiety. Interviewing for panic was prompted by her mother’s recollection of the supply closet story.
In view of Ms. B’s cooperativeness and supportive family, outpatient treatment of her recent-onset psychosis began with aripiprazole, 10 mg/d, and clonazepam, 0.5 mg every 12 hours. Clonazepam was gradually increased until voices (and panic) ceased. She was then able to describe how earlier panics had felt just like voices, but without the voices. The fears of strangers continued. Escitalopram, 20 mg/d, was added for social anxiety (aripiprazole enhances the benefits of selective serotonin reuptake inhibitors).
One month later, her fears of strangers diminished, and she felt more comfortable around people than ever before. On the same medications, and in psychotherapy over the next year, she began to increase her social network while making plans to start college.
Larger studies are needed
Current research supports the concept of a 5-diagnosis classification of psychoses, which may correlate with our comorbid anxiety and depression model. Larger diagnostic and treatment studies would invaluably examine existing research and clinical experience, and potentially encourage more clinically useful diagnoses, specific treatments, and improved outcomes.
Bottom Line
New insights from evolutionary psychopathology, clinical research and observation, psychotogenesis, genetics, and epidemiology suggest that most functional psychoses may fall into 1 of 5 comorbidity-defined subtypes, for which specific treatments can lead to much improved outcomes.