Differential Diagnosis of Psychosis

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Differential Diagnosis of Psychosis

By / Featured Articles, Lectures, Teaching / No Comments / March 14, 2022

David L. Fogelson, M.D.

Clinical Professor of Psychiatry

David Geffen School of Medicine at UCLA And The Semel Institute for Neuroscience and Human Behavior at UCLA.

Psychosis

  • psychosis (n.)
  • 1847, “mental derangement,” Modern Latin, from Greek psykhē “mind” (see psyche) + -osis”abnormal condition.” Greek psykhosis meant “a giving of life; animation; principle of life.“
  • In its modern lay form it means abnormal condition of the mind
  • 1980 DSM-III it was defined as gross impairment in reality testing
    • Incorrect interpretation of one’s own perceptions and thoughts and thus making incorrect inferences about external reality
    • These are major distortions of reality
    • Psychosis consists of hallucinations or delusions without insight they are incorrect inferences about external reality
    • DSM-III allowed that grossly disorganized behavior might also represent psychosis
  • DSM-IV
    • Narrow definition: delusions or prominent hallucinations, with the hallucinations occurring in the absence of insight into their pathological nature.
    • A slightly less restrictive definition would also include prominent hallucinations that the individual realizes are hallucinatory experiences.
    • Broader still is a definition that includes other positive symptoms of Schizophrenia (i.e., disorganized speech, grossly disorganized or catatonic behavior).  
  • DSM-5
    • Keeps definition simple: hallucinations, delusions, and formal thought disorder
  1. Psychoses due to medical conditions
  2. Toxic Psychoses
  3. Idiopathic psychoses (DSM-5 Disorders)
    Complications include: substance abuse, suicide (up to 15% in untreated patients), victimization, rare violence

Group 1: Psychoses due to medical conditions

  • Para neoplastic syndromes
  • Neurologic Conditions
    • Degenerative diseases: Huntingtons, Dementias
    • CNS neoplasms
    • CNS neoplasms
    • Auotimmune Disorders: Multiple Sclerosis, Lupus
    • Epilepsy & Neurologic Migraines
  • Rare Genetic Disorders: Porphyria
  • Endocrine: thyroid, parathyroid, adrenocortical
  • Metabolic: hypoxia, hypoglycemia
  • fluid/electrolyte imbalances
  • Hepatic/renal disease
  • Infectious Disease
    • Lyme’s
    • Syphilis
    • HIV

Group 2: Toxic Psychoses

  • Substance abuse, acute & withdrawal effects: alcohol, THC, hallucinogens, phencyclidine, inhalants, sedatives, anxiolytics, stimulants:
  • Prescribed Medications: antibiotics, anticholinergics, anesthetics, analgesics, anticonvulsants, antihistamines, antihypertensive and cardiovascular, antimicrobial, antiparkinsonian, chemotherapeutic agents (e.g., cyclosporine and procarbazine), glucocorticoids, gastrointestinal, muscle relaxants, nonsteroidal antiinflammatory drugs, other over-the-counter medications (e.g., phenylephrine and pseudoephedrine), antidepressant medications, and disulfiram.
  • Toxins: organophosphate insecticides, nerve gases, carbon monoxide, carbon dioxide, anticholinesterase

Group 3: DSM-5 Psychotic Disorders Defined by Clinical Syndromes: Delusional Disorder

  • Presence of delusions >1 month
  • Never met Criterion A for schizophrenia
    • Delusions not accompanied by auditory or visual hallucinations (tactile or olfactory okay), disorganized speech, grossly disorganized or catatonic behavior, or negative symptoms
    • Functioning not affected except for immediate consequences of the delusions
      • hiding from imagined pursuers
      • preparing to contact an imagined lover of high status
    • Mood episodes must be much briefer in duration than the delusions
      • Does not meet criteria for psychotic mania/depression
    • Not due to a medical condition or drug abuse/medication.
  • Delusions classified by type
    • Erotomanic: the belief another person, often of higher status, is in love with the patient.
    • Grandiose: of power, wealth, importance, relationships to famous people, a prophet of God, being a deity
    • Jealous: one’s spouse or partner is unfaithful.
    • Persecutory: conspiracy against/imagined mistreatment
    • Somatic: illness or deformity
    • Mixed: two or more subtypes present
  • Prevalence .18%

DSM-5: Psychotic Disorders Defined by Clinical Syndromes, Brief Psychotic Disorder

  • 1 or more psychotic symptoms with sudden onset and full remission within one month
    • Delusions/Hallucinations/Disorganized Speech (frequent derailment or incoherence)/Grossly disorganized or catatonic behavior
  • Minimum duration 1 day, maximum duration less than 1 month
  • Lifetime Prevalence .05%

DSM-5: Psychotic Disorders Defined by Clinical Syndromes, Schizophreniform

  • 2 or more psychotic symptoms persisting for a significant portion of one month and must include: hallucinations/delusions/disorganized speech
    • Delusions
    • Hallucinations
    • Disorganized Speech (frequent derailment or incoherence)
    • Grossly disorganized or catatonic behavior
    • Negative Symptoms (diminished emotional expression or avolition)
  • Duration 1-6 months
  • Prevalence .07%
  • lifetime prevalence .58%
  • the patient must have 2 or more of the following symptoms:
    • Delusions
    • Hallucinations
    • Disorganized speech (incoherence or derailments into tangents)
    • Disorganized or catatonic behavior
    • Negative symptoms (flattening of affect, muteness, loss of volition)
  • At least 1 of the symptoms must be the presence of delusions, hallucinations, or disorganized speech.
  • Continuous Sxs > 6 months
    • at least 1 month of active symptoms (or less if successfully treated), with social or occupational deterioration
  • Subtypes removed as unhelpful; did not better-target treatment or predict treatment response.
  • Etiology: genetic and environmental factors affecting neuro-development

DSM-5: Psychotic Disorders Defined by Clinical Syndromes, Schizoaffective Disorder

  • Lifetime Prevalence: .32%
  • A. A Major Mood Episode (Major Depressive or Manic) concurrent with Criterion A of Schizophrenia. Note: The Major Depressive Episode must include Criterion A1, pervasive sadness, emptiness, hopelessness or tearfulness.
  • B. Delusions or hallucinations for > 2 weeks in the absence of a Major Mood Episode (Depressive or Manic) during the lifetime duration of the illness.
  • C. Symptoms meeting criteria for a Major Mood Episode present for the majority of the total duration of the active and residual portions of the illness.

Specify whether:

  • Bipolar Type: if a Manic Episode is part of the presentation. Major Depressive Episodes may also occur.
  • Depressive Type: Only Major Depressive Episodes are part of the presentation.
  • With catatonia with > 3 Sxs: catalepsy, waxy flexibility, stupor, agitation, mutism, negativism, posturing, mannerisms, stereotypies, grimacing, echolalia, and echopraxia.

DSM-5: Psychotic Disorders Defined by Clinical Syndromes, Psychotic Mania/Depression

  • Lifetime Prevalence: .12-.33%
  • Psychotic Symptoms during a mood episode (hallucinatiions/delusions)
  • Psychotic Symptoms are never present for 2 weeks or more in the absence of a mood episode
  • Psychotic Sxs in a Depressive episode have themes of guilt, worthlessness, decay, persecution, poverty, deserved punishment, extreme hopelessness,
  • Psychotic Sxs in a Manic episode include delusions of reference, grandiose delusions, hallucinations of God’s voice, persecutory delusions,

DSM-5: Psychotic Disorders Defined by Clinical Syndromes, Postpartum Psychosis

  • Lifetime Prevalence: .2% of live births
  • Most often in a patient with a history of Bipolar Disorder but also in patients with Sz, Sz-affective, & Psychotic Depression
  • Hallucinations/Delusions within 6 weeks Postpartum
    • Often with thought disorganization
    • Often with bizarre behavior
    • Sometimes with frank delirium with disorientation X 3
  • Etiology: hormonal factors and genetic vulnerability
  • Comorbid depression/mania is common
  • .2% commit suicide
  • 4% commit infanticide (delusions that the baby is evil)

Age of Onset of Psychotic Disorders 

  • Late Adolescence or early adulthood
    • Schizophrenia
    • Bipolar Disorder
    • Psychotic Depression
  • Middle Age
    • Delusional Disorders
  • Post Middle Age
    • Neurodegenerative Disorders

Age of onset of Secondary Psychosis

  • Can occur at any age
  • Unusual Age of onset and rapid deterioration suggest:
    • Secondary Psychosis
      • Due to medical illness
      • Due to substance abuse
      • Due to a medication
        • Never forget to rule out an iatrogenic cause for a new medical symptom
    • Clues suggesting a Secondary Psychosis
      • History of headaches; seizures; visual/olfactory/tactile hallucinations
      • Absence of a family history of psychotic disorders
        • Remember disorders do not “breed true”
        • A parent my have Schizophrenia, and a child Bipolar Disorder, and vice versa

Natural History of Idiopathic Psychoses

  • Schizophrenia, Schizoaffective Disorder, Psychotic Mood Disorders
  • Usually evolve with adolescent premorbid symptoms (schizotypal)
  • Usually insidiously progress through prodromal (schizophreniform) phase in early adulthood
  • To a full syndromal phase (ages 17-25)
  • To progressive, chronic, and residual stages
  • A marked departure of course with rapid onset (days or a few weeks) and rapid deterioration suggests a secondary psychosis

Complications and Comorbidity

  • Suicide Attempts—Lifetime Prevalence 34.5%
  • Suicides—Lifetime Prevalence 10-15%
  • Substance Abuse—Lifetime Prevalence 74%
  • Homelessness—Annual Prevalence 5%
  • Victimization by others—Annual Prevalence 13%

Increased Risk for Acts of Violence Associated with Psychosis

  • Increased odds of committing acts of violence as compared to the general population, 50%. Absolute risk is low.
    • E.g. risk of homicidal behavioral in general population is .005% v .0075% in patients with Sz
  • Less risk than individuals with Antisocial Personality Disorder/Substance Abuse
    • The combination of alcoholism and antisocial personality disorder increases the odds of women committing homicide 40 to 50 fold, while the diagnosis of schizophrenia increases the risk 5 to 6 fold
    • Patients with concomitant mental illness and substance abuse are 73 percent more likely to be aggressive than are nonsubstance abusers, with or without mental illness.
    • Patients with primary diagnoses of substance use disorders and personality disorders are 240 percent more likely to commit violent acts than mentally ill patients without substance abuse issues.

Etiology and Pathophysiology

  • Pathways mediated by Neurotransmitters
    • Dopamine, increase in postsynaptic stimulation
    • Glutamate, increase in postsynaptic stimulation
  • Anatomical Areas most implicated
    • Hippocampus
    • Midbrain
    • Corpus striatum
    • Prefrontal cortex
  • Pathophysiology of increased dopamine/glutamate postsynaptic stimulation
    • Deficiency of gamma aminobutyric acid (GABA) inhibitory interneurons
    • Subsensitive N-methyl-D-aspartate (NMDA) glutamate receptors
    • Increased synaptic levels of glutamate

Models of Psychosis: molecular compounds provoke psychosis

  • Cannabinoid-1 receptor agonists and cathinone (bath salts)modulate trafficking of dopamine and glutamate at the synapse and can induce psychotic symptoms
  • Stimulation of the serotonin receptor subtype, 5-hydroxytryptamine subtype 2A (5-HT 2A) & 1A by lysergic acid diethylamide (LSD), mescaline, & psilocybin
    • Different than psychosis induced by other agents: perceptual distortions, depersonalization
    • 5-HT2A partial agonist and 5-HT1A agonist
    • LSD stimulates D2 receptors
    • Indirect glutamatergic effects
  • Stimulation of dopamine receptors by psychostimulants, primarily paranoid delusions

Genetic Factors in Psychosis: family studies of phenotype

  • First degree relatives of Bipolar/Sz probands have 10 to 15 times the rates in the general population
  • Twin Studies demonstrate high heritability of 72%
  • 5% of first degree relatives of probands are affected compared to .5% of the general population
  • Schizophrenia Spectrum Disorders aggregate in families
    • Schizotypal Personality Disorder
    • Paranoid Personality Disorder
  • Avoidant Personality Disorder is 6X more prevalent in first degree relatives of probands with Schizophrenia
  • Speculation has been that Psychosis is dimensional and is determined in most instances by many single-nucleotide polymorphisms of small effect

Genetics of Psychosis: What is a gene? What is a SNP? Why does it matter?

  • In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function.
  • During gene expression, the DNA is copied into RNA.
  • The RNA can be directly functional or be the intermediate template for a protein that performs a function.
  • Single-nucleotide polymorphisms (SNPs)
    • common variants of individual nucleotide sequence that are frequently observed in the population (>1%).
  • The hypothesis that a few SNPs of large effect would account for most cases of SZ has been proven to be false
  • Genome-wide association studies (GWAS) have identified 108 SNPs that contribute to the likelihood of Sz, each of weak effect

Genetic Factors in Psychosis: genotype analysis, Copy Number Variants

  • Copy number variants (CNVs)
    • segment of one kilobase (kb) or larger that is present at a variable copy number in comparison with a reference genome. Insertions, deletions, or duplications
    • most widely known CNVs are the trinucleotide repeats (TNRs),
    • CNVs cover approximately 360 megabases, or 12% of the human genome. The HapMap Project notes that CNVs encompass more nucleotide content per genome than SNPs
    • Inherited or appear spontaneously de novo
    • CNVs have strong impact on risk for SZ, odds ratios of 2-57!
    • CNVs associated with SZ are not deterministic but penetrate determined by other risk variants on the genome or by environmental factors

Genetic Factors in Psychosis: genotype analysis, Polygenic Risk Score

  • Polygenic risk score
    • A polygenic score is simply an algorithm—one that adds up the impact of multiple variants (SNPs). A PRS can analyze just a few variants, or it can consider millions. The key is that these variants have to be considered in aggregate. Each SNP is weighted by its relative contribution to risk for SZ.
    • PRS’s for Sz have at least an order of magnitude greater effect than copy number variants (CNVs)
    • Increasing PRS’s are correlated with less improvement with antipsychotic medication

Am J Psychiatry 2019; 176:21–28; doi: 10.1176/appi.ajp.2018.17121363

Common SNPs, Rare Copy Number Variants, Polygenic Risk Score and the Overall Risk for Schizophrenia

  • 1.4-2.5% of individuals with SZ carry CNVs that confer risk for Sz
  • Rare copy number variants (CNVs) and common single-nucleotide polymorphisms (SNPs) contribute to liability to schizophrenia
  • Does the risk of schizophrenia require less contribution from common SNPs in the presence of a rare CNV?
  • CNVs contribution to risk was measured by those previously associated with SZ (22q11.2), with > 500 kb deletions, and aggregate total CNV burden
  • Patients with SZ carrying CNVs associated with SZ (odds ratio >15) had PRSs diminished by the effect size of the CNV
  • Risk for SZ = PRS + CNV (total burden of CNVs or large CNV)
  • CNV testing may become commercially available and help patients understand why they have a psychotic mental disorder

Am J Psychiatry 2019; 176:29–35; doi: 10.1176/appi.ajp.2018.17040467

Neurodevelopmental Factors

  • Prenatal Factors predispose to Sz
    • Maternal infections: influenza & other infections (OR=7.67)*
    • Drug Toxicity: nicotine (OR=3.41)**
    • Nutritional Deficiencies: famine during war (OR=9.52)*
    • Birth Complications: hypoxemia (OR=5.4)*
    • +Psychiatry Research: 2019 Jan;271:23-30. doi: 10.1016/j.psychres.2018.11.023. Epub 2018 Nov 13.
    • **Am J Psychiatry. 2016 Aug 1;173(8):799-806. doi: 10.1176/appi.ajp.2016.15060800. Epub 2016 May 24
  • Postnatal Factors predispose to SZ
    • Immigrant Status (OR=2-4)
      • Schizophr Bull. 2017 Oct 21;43(6):1251-1261. doi: 10.1093/schbul/sbx010.
    • Drug Abuse
      • Cannabis (OR=5.2)
      • Alcohol (OR=3.4)
      • All substance abuse combined (OR=6)
      • Psychol Med. 2017 Jul;47(9):1668-1677. doi: 10.1017/S0033291717000162. Epub 2017 Feb 7.
      • Schizophr Res. 2018 Apr;194:78-85. doi: 10.1016/j.schres.2017.04.016. Epub 2017 Apr 14

Autoimmune and Inflammatory Disorders with Psychoses: Systemic Lupus Erythematosus

  • Etiology: autoantibodies influence CNS neurotransmitter function, especially the glutamate system
  • Antibodies can be measured and disease syndromes identified
  • Systemic Lupus Erythematosus
    • In 30% of SLE patients antibodies target the  N-methyl-D-aspartate (NMDA) glutamate receptor, NR2 subunit
    • Some patients develop psychotic symptoms

Autoimmune and Inflammatory Disorders with Psychoses: Paraneoplastic

  • Paraneoplastic and Autoimmune Syndromes
    • Immune encephalitis has, as a central symptom, psychosis
    • Encephalitis due to antibodies directed against the NMDA receptor, NR1 subunit
  • Occur mainly with ovarian teratomas
  • The teratomas cause the immune system to produce antibodies that can cross the blood brain barrier
  • Antibodies are to the NMDAR1 receptor on CNS neurons

Infectious Disease Associated with Psychosis

  • Sexually transmitted diseases
    • HIV
    • Syphilis
    • Lyme’s Disease
  • Parasitic Disease-20 helminths cause brain infections
    • Neurocysticercosis (tapeworm) is most common: seizures, Increased intracranial pressure, hydrocephalus, altered mental status
      • Brain MRI: nodules, calcified cysts, hydrocephalus
      • Microscopic stool examination
      • Immunoblot assay of serum
    • Other Helminthic Brain Infections: schistosomiasis (blood flukes), echinococcal cysts (tapeworm), coenurosis (tapeworm), Gnathostomiasis (nematode larvae)

Viral Infections of the CNS

  • CNS viruses causing Encephalitis
    • Most common on MSE: confusion, agitation, hallucinations, dysarthria, loss of consciousness
    • headache, fever, myalgia, arthralgia, fatigue should raise index of suspicion
      • Herpes Viruses
        • Herpes simplex type 1
        • Varicella Zoster
        • Epstein-Barr
      • Enteroviruses
      • Mosquito Borne Viruses
        • West Nile virus
        • Equine viruses
      • Tick Borne Viruses: Powassan Virus
      • Rabies Virus
      • Measles (rubeola), Mumps and German Measles (rubella)
    • Diagnosis: Lumbar puncture, Bran MRI, Antibody Titers

Dementias Associated with Psychosis

  • Lewy Body Dementia; third most common dementia; onset >60
    • Lewy Body inclusions (alpha-synuclein) in cytoplasm of cortical neurons
    • Overlaps with Alzheimer Dementia (neuritic plaques and neurofibrillary tangles)
    • Visual Hallucinations most common but also auditory, olfactory, tactile
    • Bizarre Delusions
  • Alzheimer Dementia; 80% of dementias, onset>65
    • Polygenic
    • Mutations in amyloid, presenilin I & II
    • Persecutory Delusions
  • Fronto-Temporal Lobe Dementia; 10% of dementias, onset>55
    • Severe atrophy, neuronal loss, gliosis, Pick inclusion Bodies
    • Half are inherited, most are 17q21-22 mutations, tau protein abnormalities
    • Impulsive, lose social inhibitions, hypersexual

Basis of Establishing a Psychosis Diagnosis

  • The Gold standard remains the clinical interview
    • Biologic tests are most often performed in patients with new onset psychosis to rule out non-psychiatric disorders causing psychosis
    • Biologic tests are also used when a neurodegenerative disorder, other medical condition, or drug/medication toxicity is suspected
  • No Biologic Test is diagnostic for a Psychotic Mental Disorder
  • Neuroimaging
  • Neurophysiological
  • Serologic
  • Toxicologic
  • Genomic Sequencing

Neuroimaging

  • Magnetic Resonance Imaging (MRI), Functional Magnetic Resnonace Imaging (FMRI), and Positron Emission Tomography (PET) have found abnormalities in patients with psychotic mental disorders
  • Schizophrenia, Schizoaffective Disorder, Bipolar Disorder with Psychosis
    • Focal volume reductions in temporal, frontal, and parietal lobes
    • Reduced cortical thickness in same areas and other areas
  • In Sz, PET demonstrates:
    • Increased synaptic dopamine levels in the ventral striatum
    • synaptic dopamine levels in the frontal cortex
  • In Sz, magnetic resonance spectroscopy (MRS) demonstrates:
    • Increased glutamate levels in prefrontal cortex and medial temporal regions
  • These findings are NOT sensitive or specific enough to aid in diagnosis and therefore neuroimaging should not be routinely used in the clinic unless the psychosis is thought to be secondary to another medical disorder

Neurophysiological Tests: The EEG, Epilepsy, Evoked Potentials and Psychosis

  • Event Related Potentials are abnormal in patients with psychotic disorders
    • EEG is used to measure evoked potentials elicited by a variety of sensory, motor, and cognitive stimuli
    • They lack the sensitivity and specificity to be useful in clinical practice
  • Epilepsy and Psychosis
    • Psychosis can be linked temporally to ictal, postictal and interictal periods
    • The symptoms resemble Schizophrenia
    • Some antipsychotic medications lower the seizure threshold
    • Some antiepileptic medications cause psychotic symptoms
    • EEG is indicated when a seizure disorder is suspected

Epilepsy and Psychosis: a practical approach

Pract Neurol. 2018 Apr;18(2):106-114. doi: 10.1136/practneurol-2017-001775. Epub 2017 Dec 22.

  • Temporal Lobe Epilepsy has the highest prevalence of psychosis, 10%-15%
  • Other risk factors for psychosis
    • Uncontrolled seizures
    • Hippocampal sclerosis associated with seizures
    • Neurodevelopmental disorders associated with seizures
    • Early age of onset of epilepsy
    • History of status epilepticus
  • Neurobiology and neuroanatomy of Epilepsy and Psychosis
    • Temporal lobe epilepsy
      • Reduced dopamine binding capacity of D2 & D 3 receptors in striatum
    • Reduced Prefrontal dopamine activity may also predispose to seizures

Epilepsy and Psychosis: Making the Diagnosis

Pract Neurol. 2018 Apr;18(2):106-114. doi: 10.1136/practneurol-2017-001775. Epub 2017 Dec 22.

  • Postictal Psychosis associated with temporal lobe seizures
    • Persecutory delusions, grandiose delusions, somatic delusions
    • Aggressive with directed violence
    • Duration 1-12 weeks
  • Postictal Psychosis may be associated with other forms of seizures
  • Ictal Psychosis
    • Duration is limited to the active seizure
    • Bizarre behavior, incoherence, without loss of consciousness

Serologic Tests and Toxicologic Tests

  • Serologic Tests
    • Syphylis: (RPR screen with reflex antibody testing)
    • HIV (HIV-1/2 Antigen and Antibodies)
    • Lyme’s Disease (Lyme Disease Antibody Index of CNS Infection, CSF)
    • Systemic Lupus Erythematosus (ANA Screen)
    • Neurocysticercosis (Cysticercus Antibody, Enzyme Linked Immunosorbent Assay [ELISA]with reflex Western Blot)
    • Antibody titers for viruses
      • Antibody titers for Herpes Viruses
        • Herpes simplex type 1
        • Varicella Zoster
        • Epstein-Barr
      • Enteroviruses (enteroviruses RNA, Real-Time Polymerase Chain Reaction–RT-PCR)
      • Mosquito Borne Viruses
        • West Nile virus (antibody test)
        • Western Equine Encephalitis virus antibodies, CSF
      • Tick Borne Viruses: Powassan Virus; neuro-invasive encephalitis
      • Rabies Virus (Rapid Fluorescent FOCI Inhibition Test)
      • Measles (rubeola), Mumps and German Measles (rubella)—antibody panel
    • Antibody titer for NMDAR1
  • Toxicologic Tests: urine and blood screening
    • Alcohol, amphetamines, cannabis, benzodiazepines, opiates, hallucinogens

Treatment

  • Neuroleptics: blockade of the D2 receptor
    • Seldom used: haloperidol (Haldol), perphenazine (Trilafon), fluphenazine (Prolixin), thiothixene (Navane), and others
    • More Prone to Extrapyramidal Neurologic Side Effects (EPS) & Tardive Dyskinesia (TD)
  • Atypical Antipsychotics: blockade of D2, 5HT2A Partial Agonists
    • More prone to Metabolic Syndrome
    • Less prone to EPS and TD
  • Pimavanserin (Nuplazid): inverse agonist and antagonist at serotonin 5-HT2A, 5-HT2C receptors; primarily for Parkinson’s related psychosis
    • Neuromodulation: TCMS & ECT
      • ECT can be used in psychotic mood disorders, catatonia, and Sz
      • TCMS has been applied to treatment of auditory hallucinations
    • Psychotherapies

Treatment: Atypical Antipsychotic Medications

  • Aripiprazole (Abilify)
  • Asenapine (Saphris)
  • Brexpiprazole (Rexulti)
  • Cariprazine (Vraylar)
  • Clozapine (Clozaril)
  • Iloperidone (Fanapt)
  • Lurasidone (Latuda)
  • Olanzapine (Zyprexa)
  • Paliperidone (Invega)
  • Quetiapine (Seroquel)
  • Risperidone (Risperdal)
  • Ziprasidone (Geodon)

Transcranial Magnetic Stimulation (TMS) for Sz

Cochrane Schizophrenia Group 2015

  • Conclusions
    • Insufficient Evidence to support or refute effectiveness
    • Evidence was not unequivocal
    • No evidence that TMS was an effective adjunct to medications
    • Overall quality of clinical trials was poor
      • Risk of bias in ratings was present
    • Number of subjects was small
    • No standard for stimulation intensity, stimulation length, brain targets
    • No standard scales used between studies
    • Need standardized treatment protocols and measures for future studies to allow meta-analyses
    • More recent studies suggest efficacy but subject number remains small

Electroconvulsive Therapy Added to Non-Clozapine Antipsychotic Medication for
Treatment Resistant Schizophrenia: Meta-Analysis of Randomized Controlled Trials
Zheng W Plos One 2016

  • Randomized Controlled Trials of ECT & Antipsychotic Med
  • 11 studies, n=818, 10 weeks in duration
  • ECT was superior to monotherapy with a medium effect size
    • Symptom response as early as day 10
    • NNT 6
    • ADRs: headache and memory impairment
    • Mean #of ECT rxs 14
    • Bilateral lead Placement
    • Caution: no data on neurocognitive outcomes
  • Data is insufficient in regards to ECT augmentation of Clozapine

Editorial: Non-pharmacological Interventions for Schizophrenia: How Much Can Be Achieved and How?  Andreou & Moritz, Front Psychol 2016

  • Peters et al 2016 provide corroborating evidence that CBT is effective in routine delivery service venues, not just academic institutions.
  • Mehl et al 2016 perform an updated meta analysis of CBT for delusions & confirm findings of Burns et al 2014, but indicate other psychotherapies may be equally effective
  • Moritz et al 2016, So et al 2016, & Balzan 2016, report that metacognitive training addressing reasoning biases associated with emergence of delusions can
  • Moderate bias
  • Improve delusions
  • Enhance Medication Compliance
  • Other approaches with less evidence base include
  • Social cognitive training
  • Mindfulness training
  • Family Therapy
  • Future Directions: psychotherapy directed at depression and social anxiety