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Jordan Calabrese

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Phillip Hynes
Sandeep Sekhon

10/27/2019 7:48:28 AM


Psychosis is an amalgamation of psychological symptoms resulting in a loss of contact with reality. The current thinking is that although around 1.5 to 3.5% of people will meet diagnostic criteria for a psychotic disorder, a significantly larger, a variable number will experience at least one psychotic symptom in their lifetime.[1] Psychosis is a common feature to many psychiatric, neuropsychiatric,[2][3][4] neurologic, neurodevelopmental, and medical conditions. It is the hallmark feature of schizophrenia spectrum and other psychotic disorders, a co-occurring aspect to many mood and substance use disorders,[5] as well as a challenging symptom to many neurologic and medical conditions. Psychosis can result in high levels of distress for patients and loved ones, which is why it has become a primary target of treatment for medical professionals.


Psychosis may result from a primary psychiatric illness, substance use, or another neurologic or medical condition. Brain abnormalities have correlated with first-episode psychotic disorders, including reduced prefrontal, superior, and medial temporal grey matter.[6] Primary psychotic disorders are considered neurodevelopmental abnormalities and believed to develop in utero, although many times the manifestation of psychotic symptoms and full-blown illness correlate with epigenetic or environmental factors (substance abuse, stress, immigration, infection, postpartum period, or other medical causes). There is significant evidence for genetic risk factors in the pathogenesis of psychotic disorders.[7]


The incidence of a first-time episode of psychosis is approximately 50 in 100000 people, while the incidence of schizophrenia is about 15 in 100000 people.[8] The peak age of onset for males is teens to mid-20s, while for females, the onset tends to be teens to late-20’s. Earlier onset correlates with poorer outcomes, although early intervention correlates with better results. Psychosis is extremely uncommon in children.


Most strongly linked to the pathophysiology of psychotic disorders is the neurotransmitter dopamine. The positive symptoms of psychotic disorders are believed to be caused by excess dopamine in the mesolimbic tract. Glutamate, an excitatory neurotransmitter, is also implicated. Multiple studies have found a decreased function of the N-methyl-D-aspartate (NMDA) glutamate receptor.[9][10] Studies have also pointed to gamma-amino-butyric acid (GABA), an important inhibitory neurotransmitter.[11] Some studies show evidence of dysfunction in patients with subjects with schizophrenia. Lastly, implications point to an imbalance in acetylcholine.[12][13] This finding developed while observing the smoking behaviors of patients with schizophrenia, as nicotine has been shown to increase acetylcholine function. Observers noted some improvements in deficits in the smokers, and cognition was improved in studies as well.[14]

History and Physical

The Diagnostic and Statistical Manual; fifth edition (DSM-V), the principal authority on psychiatric diagnoses, strays from offering a hard definition of “psychosis.” Rather, it allows for psychotic disorders, primary or medically related, to be defined by abnormalities in one of the following five domains, which this activity will discuss in detail below. It will be useful to consider these five categories when the term “psychosis” arises in a medical setting.

  • Delusions
  • Hallucinations
  • Disorganized thought
  • Disorganized behavior
  • Negative symptoms

Delusions are fixed, false beliefs for which a person lacks insight into, even in the face of evidence that proves contrary to their validity. A variety of different types of delusions exist. Persecutory delusions are the most common; this is where one believes someone or something is out to get them. Referential delusions are beliefs that things the patient sees and hears in the external environment are directed at them. Grandiose delusions are grand, magnificent, and self-inflating, yet unrealistic, views of oneself. Erotomanic delusions are when one believes others are in love with them. Nihilistic delusions are when one believes major catastrophes will occur. Somatic delusions are false beliefs regarding one’s own or other peoples body function. We can further separate delusions into two main categories: Bizarre and non-bizarre. Delusions are bizarre when they are outside the realm of possibility and defy the laws of the physician universe. For example, “Flying mutant alien chimpanzees have harvested my kidneys to feed my goldfish.” Non-bizarre delusions are potentially possible, although extraordinarily unlikely. For example: “The CIA is watching me 24 hours a day by satellite surveillance.” The delusional disorder consists of non-bizarre delusions.

Hallucinations are perceived experiences in the absence of an external stimulus sufficient to evoke such experience. By definition, they are not under voluntary control. Hallucinations may occur under any sensory modality (visual, auditory, olfactory, gustatory, proprioceptive, tactile, etc.), although auditory hallucinations are the most common in the schizophrenia spectrum disorders. Subjects usually experience these as voices “outside” one's head. Visual and tactile hallucinations predominate in severe alcohol withdrawals. Visual hallucinations are also a hallmark feature of Lewy body dementia.

Disorganized thought usually gets illuminated through the patient’s speech and general communication patterns. In a mental status examination, one should be able to say a person not suffering from a psychotic disorder exhibits a “logical” and “goal-directed” thought process. In psychosis, one can see loosened associations or sequences of unrelated or loosely related ideas. Circumstantial thought, or a “non-linear thought pattern,” is where a person is unable to give a direct answer to a question without excessive or unnecessary detail. Tangential thought is where a person continually drifts from the topic of conversation, never to return to the original point. Word salad is an unintelligible or incoherent jumble of words. Neologisms are made up of words or phrases. Perseveration is the repetition of words and statements.

Disorganized behavior consists of a broad spectrum of faulty goal-directed activity, which will usually lead to a decline in daily functioning. In psychosis, it is common to see patients with unpredictable and/or inappropriate emotional responses that are incongruent with the current situation; this may present as a lack of inhibition and lack of impulse control. Sometimes patients can be found performing nonsensical actions that would largely be considered socially inappropriate. Catatonic behavior appears as a notable decrease in reactivity to the external environment, which can consist of psychomotor retardation, immobility, and severe rigidity with a lack of verbal response, to an excitatory state of aimless and unrestricted motor activity.

Negative symptoms are a decrease or loss in normal functioning, and its components can commonly be confused with those of depressive disorders. The prodrome phase of schizophrenia commonly presents with negative symptoms. Patients can present as inexpressive or emotionally blunted, and can be described as having a “flat affect.” They can exhibit simplistic or prosodic speech patterns, along with alogia (poverty of speech). Psychomotor retardation, lack of energy, interest, concentration, and pleasure in activities once found pleasurable (anhedonia) are all potential features as well.


As with any other medical or psychiatric condition, the interview is of the utmost importance for guiding the treatment plan. As usual, one starts by obtaining a thorough history. The history should include but is not limited to the following: Timeline and severity of symptoms, prior psychiatric history/conditions, hospitalizations, previous medical history/conditions, medications taken (psychiatric and non-psychiatric), history of substance use, detailed social history, history of trauma (emotional, physical, sexual), suicidal ideation with prior attempts, auditory/visual hallucinations. The clinician should also be able to recognize the psychiatric patient may not always be able to give the most concise history due to their underlying condition.

Of equal importance to the history, and an indispensable component of the psychiatric interview is the mental status exam (MSE). One must make a careful observation regarding the patient’s appearance, behavior, speech, mood, affect, thought process, and thought content.

Aside from a urinary toxicology screen, a standard medical workup can help to rule out non-psychiatric causes of psychosis, as well as some additional tests if clinical suspicion permits. These may include:

  • Complete blood count and metabolic panel
  • Urinalysis, urine cultures
  • Thyroid-stimulating hormone (TSH), T3, T3
  • Liver function tests
  • Vitamin B12
  • HIV
  • CT, MRI
  • EEG
  • Lumbar puncture
  • Rheumatologic or immunologic workup

It is important to note that some substances which correlate to psychotic episodes (bath salts, certain synthetic strains of cannabis, psychedelics) may not show up on basic drug screen panels.

It is only when clinicians have officially ruled out a substance, medication-induced, or other underlying medical causes that one can consider a primary psychotic disorder.[15]

Treatment / Management

The management of a psychotic patient varies greatly depending on the origins of the psychosis. A psychiatrist should evaluate any patient experiencing an episode of psychosis. Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders, and the choice, dosing, and administration of the medication will largely depend on the scenario.

Antipsychotics are generally the treatment for schizophrenia spectrum disorders. Initial dosing should be at a low dose and titrated up as needed. Of note, there has been long-standing debate as to whether second-generation antipsychotics are more efficacious than the first generation.[16][17][18]

Antipsychotics have also been shown to be most effective in treating the psychotic symptoms of drug-induced psychosis, mania, delirium,[19] the psychotic features of depression, as well as the psychotic features of dementia and other neurologic conditions. Of course, beyond the acute psychosis, treating the underlying cause is always an appropriate course of action.

Antipsychotic medications have demonstrated to be most effective in positive symptoms of psychosis discussed earlier (hallucinations, delusions, disorganized thoughts, and behavior) and less useful for negative symptoms.[20] They can also demonstrate significant side effects, including extrapyramidal symptoms and dangerous QT prolongation. Of note, clozapine and olanzapine specifically have been shown to reduce the risk of suicide in psychotic patients.[21]

Benzodiazepines have evidence as an effective treatment for catatonic symptoms of psychosis.  

Along with medications, family and caregivers also play an important role in the management of a psychotic patient, including providing a safe and therapeutic environment for the patient, as well as interacting with them in and calm, empathetic manner.[22]

In the scenario of an agitated, potentially aggressive, acutely psychotic patient at risk of harming themselves or someone else, they should be hospitalized and placed in the care of health care professionals. An injectable form of a typical antipsychotic with a benzodiazepine is most effective in this case.[23] Physical restraints should be avoided at all costs and correlate with increased mortality.

Along with medications, cognitive behavioral therapy can play an integral role in the treatment of patients with psychotic symptoms.[24]

Lastly, it is critical to note that for acute onset psychosis in patients, ultimately developing a schizophrenia-spectrum psychotic disorder, early intervention may improve clinical outcomes. Delays in treatment have statistical links with poorer treatment outcomes.[25]

Differential Diagnosis

To differentiate between psychoses associated with a primary psychotic disorder and psychotic disorders associated with other medical or neurologic conditions, one can examine the following factors:

Age of onset: This is one of the most important factors when determining the etiology of a psychotic episode. The primary psychotic disorder will usually present in late teens to the early thirties. (Men typically present with the condition earlier than women). Psychosis associated with medical/neurological conditions will often present after the age of 40. The older the patient, the higher the risk for medical or neurological psychosis, especially in the hospital setting.

The pattern of onset: Primary psychotic disorder may present subtly, often with a prodromal phase that may be confused with another psychiatric disorder (e.g., schizophrenia can easily be confused with depression in its initial stages). Medical or neurological psychosis will usually present acutely.

Genetics: There is a significant association with the primary psychotic disorder and family history than psychosis associated with medical/neurologic conditions.

Presentation: Primary psychotic disorder commonly presents during significant life stressors (moving, new job, end of a relationship), while psychosis associated with medical/neurologic conditions generally presents in healthcare settings.

Hallucinations: Primary psychotic disorder is generally synonymous with auditory hallucinations, whereas psychosis associated with medical/neurologic conditions usually correlates with all other types of hallucinations except auditory (e.g., visual, tactile, olfactory).

Specific primary psychotic disorders, with their subtypes, along with all other psychotic disorders, will be discussed in detail in other activities.


The course for schizophrenia was once believed to be unvaryingly poor, although now studies have shown there is potential for good outcomes. The multitude of newer medications, along with an option for long-acting injectable antipsychotics, has given patients a variety of treatment options along with addressing compliance issues. As stated earlier, early intervention, along with intensive treatment, seems to be of utmost importance in long-term outcomes. There is little data supporting evidence either way for a single psychotic episode related to a medical or neurologic condition, and prognosis would be condition dependent. Treating the current episode, along with the underlying illness, would be considered the best course of action.


In any psychotic episode, regardless of etiology, there is always risk danger to self or others. These patients require admission to a safe and therapeutic medical setting. Involuntary admission criteria will vary by state/country.

Paranoia, fear, suspicion, or other symptoms of psychosis may prevent a patient from getting the help they need initially, as well as hinder their capability for medication and treatment compliance.

There are significant side effects with antipsychotic medications, which may include extrapyramidal symptoms (EPS), metabolic syndrome, cardiac abnormalities, anticholinergic effects, sexual side effects, tardive dyskinesia, and many more.

Psychotic disorders can lead to significantly decreased daily functioning, along with an increased risk of suicide compared to the general population. The suicide rate in patients with schizophrenia is about 5%.[26]

Pearls and Other Issues

  • Psychosis is a constellation of symptoms resulting in a loss of touch with reality.
  • From 1.5 to 3.5% of people will meet the criteria for a primary psychiatric disorder in their lifetime, while many more will experience some variation of psychotic symptoms.
  • Abnormalities of temporal grey matter have a link to first-episode psychosis.
  • Initial psychotic episodes correlate epigenetic or environmental stressors.
  • A psychotic episode or disorder will result in the presence of one or more of the following five categories: delusions, hallucinations, disorganized thought, disorganized behavior, negative symptoms.
  • The incidence of a psychotic episode is around 50 in 10000 people.
  • The peak onset of a psychotic disorder is earlier in males than females.
  • Dopamine, glutamate, GABA, and acetylcholine are all neurotransmitters implicated in psychosis.
  • "Bizarre" delusions are not plausible. "Non-bizarre" delusions are often extraordinarily unlikely, but possible.
  • A detailed history and mental status exam (MSE) are critical for arriving at a diagnosis.
  • A urine toxicology screen, along with standard medical workup, can help to rule out the non-psychiatric cause of psychosis. Remember, not all drugs will show up on screening.
  • Differentiating between primary psychotic disorders, and psychotic disorders associated with another medical or neurologic condition: Age of onset, the pattern of onset, genetics, presentation, hallucinations.
  • The prodromal phase of schizophrenia is often confused with major depressive disorder.
  • A psychiatrist should always evaluate a patient experiencing a psychotic episode.
  • Antipsychotic medications are the gold-standard treatment for psychotic episodes and disorders.
  • Antipsychotics have been shown to be more efficacious in treating positive symptoms.
  • Antipsychotics can have significant side effects (QTc prolongation, EPS, metabolic syndrome, sexual side effects, tardive dyskinesia, etc.).
  • Clozapine and olanzapine are the only antipsychotics shown to decrease suicidality in psychotic patients.
  • A safe and therapeutic environment, with calm, empathetic patient interactions, are essential for treating psychotic symptoms.
  • There is potential for positive outcomes in patients with psychotic disorders.
  • Early intervention is essential for good long term outcomes.
  • Patients with schizophrenia demonstrate increased risk for suicide compared to the general population.

Enhancing Healthcare Team Outcomes

Psychosis is a common, yet extremely, distressing set of symptoms that healthcare providers will undoubtedly face at some point in their training or practice. As discussed, there is a myriad of underlying causes for a patient presenting with a psychotic episode, including a primary psychiatric disorder, substance-induced, neurologic, or medical induced. A proper medical workup, along with a psychiatric evaluation, is always warranted.

While it is possible to treat the initial symptoms of a patient experiencing an episode of psychosis, individual patients, especially those with primary psychotic disorders, will generally require ongoing care for the remainder of their lifetime. Many times, the standard treatment is not enough and does not address the subjective psychosocial stressors a patient may be experiencing. Patients with severe mental illness experience high treatment dropout rates. New, emerging studies focus on how healthcare providers can enhance healthcare team outcomes through community engagement.

Specific subgroups of patients experiencing mental illness have been historically difficult to engage: those with first-episode psychosis, homeless populations, and those with comorbid substance use. Poor treatment engagement correlates with poor clinical outcomes, relapse, and re-hospitalization. A recent emphasis on “interpersonal” care has emerged in mental health treatment, putting the context of the individual’s needs, wants, hopes, dreams, culture, and spirituality above those of their specific symptoms. The promulgation of this concept centers on training of “treating the whole patient,” and it firmly holds for patients with mental illness. This activity will focus below on three emerging, innovative, recovery-oriented techniques for engagement.[27]

Implementing Technology

Technology can serve as a medium for more significant lines of communication among people. It may assist in helping to connect with others experiencing a similar illness or hardship without facing the potential shame or guilt of seeking help in person. Some people would like to seek assistance in person, but due to limited access due to geographical location, may be unable to. Communication through technology may also be more feasible economically, particularly in the uninsured population, or those lacking funds for transportation. Online support groups or forums may also provide for a 24/7 safe haven for patients as well as creating a sense of belonging. The majority of young adults use social media and maybe more amenable to seeking help in this fashion. Being able to touch base with a healthcare professional may decrease unnecessary hospitalizations.

Peer Support

Some studies report some patients who have difficulty complying with treatment and may be untrustworthy of authority figures. Other patients may feel judged, marginalized, or stigmatized when engaging in traditional healthcare settings. Peer provider networks have emerged as a way to engage with patients and address their particular needs as well provide them with a relatable social network. Patients have noted to experience an increased sense of self-determination, self-awareness, and positive effects on engagement. Patients also feel like they finally have someone advocating for them. Studies have shown that patients receiving peer support, in the beginning, had been more engaged and motivated with treatment six months from the start. Peer support groups were shown to be particularly crucial for Army and combat veterans, specifically decreasing internal and external stigma.

Cultural Formulation

Mentally ill from ethnic minority groups are less likely to engage in mental health treatment than non-Hispanic whites. A patient’s cultural background may shape the way they perceive mental illness and may hinder their desire to seek treatment. Thus, providing culturally sensitive care is of utmost importance. The cultural formulation interview (CFI) is a 16 item questionnaire new to the DSM-V that not only seeks to understand cultural and social structures but individual circumstances as well. This approach may enhance cross-cultural communication and may help providers understand the precise needs/goals of the patient.

Evaluation and treatment/management of psychosis requires an entire interprofessional team approach. While clinicians (MDs, DOs, NPs, and PAs) may be the first to evaluate the patient, specialists will almost of necessity be involved also. This group would include psychiatrists and other mental health providers. They must communicate with each other as well as with the patient's family if there is one. Given the extensive adverse event and numerous drug-drug interactions of many antipsychotic medications, pharmacists will also need extensive input into the patient's therapy regimen and must have access to the clinicians and nurses on the case to report any concerns or findings. Nursing will often assume a caretaker role, especially with institutionalized patients, and may often have the most one on one contact daily than anyone else on the team. They need to be alert for signs of medication concerns, as well as therapeutic failure and have an open communication line to the pharmacist and especially the treating physicians. The entire interprofessional team must communicate and collaborate to bring about optimal outcomes in cases of psychosis. [Level V]

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Psychosis - Questions

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A 26-year-old female is referred by her parents, stating "strange" behavior recently. The patient is a graduate student earning her Ph.D. in aerospace engineering. They report that for around the past year, the patient has been extremely stressed about school. About eight months ago, her boyfriend of 6 years left her, stating that she put "all of her time into school." The parents became worried when they had not heard from her daughter in a few weeks, so they drove to where she lives to find her apartment in shambles, smelling horrible with “months worth of trash” piled up. They state the patient appeared as though she was “not herself.” On interview, the patient states she does not need to go to class anymore, as her field of study is “the devil’s work.” She also stated, “The voices tell me everything I need to know.” The patient has an aunt and cousin with schizophrenia. This is the first time this has happened. Medical workup was within normal limits, and urinary toxicology was negative. What is the most important part of management in the treatment of this patient?

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A 37-year-old female with no past psychiatric history was recently admitted for depressive symptoms and suicidal ideation after her and her husband had a divorce 3 weeks ago. On admission, the patient appeared sad, disheveled, and exhibited psychomotor retardation. She made poor eye contact and spoke very little. Medical workup was withing normal limits. On evaluation, she is laying on her back in bed, staring at the ceiling, and left arm is pointing straight up towards the ceiling. Her arm is rigid when there is an attempt to move her arm. What would be the next step in management of this patient?

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A 56-year-old with a past psychiatry history of schizoaffective disorder, depressed type, presents to the emergency room after attempting to jump off a bridge. The patient managed to survive with only a fractured left femur and a minor concussion. On evaluation by the inpatient provider, the patient reports experiencing auditory hallucinations telling him to do it. It was discovered the patient was taking aripiprazole at the time and has been compliant with his medications. This is the patient’s third suicide attempt in 2 years. What would be the next step in the management of this patient?

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A 17-year-old male college student presents to the emergency department appearing disheveled with poor hygiene and a bizarre, flat affect. The patient is withdrawn, makes poor eye contact, and exhibits poor hygiene. His friend found him in his room after noticing he had not been to class for the past two weeks. The friend states he knows the patient has been experiencing a recent bout of depression but was unsure as to how long has this been going on. The friend reports the room was messy and there were numerous bible verses written all over the walls, along with elaborate drawings of extraterrestrials. When he arrived, he saw the patient standing up, staring at the wall and mumbling incoherently to himself. Upon questioning, the patient intermittently looks over his shoulder. When asked if he was hearing any voices, he does not confirm, but whispers to the interviewer: “The green people are after me.” He has no known history of psychiatric illnesses. Family psychiatric history is notable for an uncle with schizophrenia. Urinary toxicology is negative, and medical workup is within normal limits. A medication is prescribed, and the most common side effects are explained; weight gain being one of the most common side effects. Which of the following symptoms will this medication help with the most?

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A 67-year-old female with no significant medical history is brought in by her son after reportedly acting “strangely” for the past few months. Urinary toxicology is negative, and medical workup is within normal limits. The patient only takes medication for her blood pressure. Which of the following, if reported by the patient, would be considered a non-bizarre delusion?

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A 55-year-old male with a history of schizophrenia is brought to the hospital for bizarre behaviour outside a public library. When police arrived, the patient was laughing hysterically while running in circles and shouting "I am the chosen one!" When asked what he was doing, he was unable to give a coherent response but would mumble made-up words. The patient also mentioned several times that he hears "them" talking to him. Given the current presentation, which of the following elements of psychosis is the patient experiencing?

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An 18-year-old male with no past medical or psychiatric history is brought to the office by his mother for “depression.” The patient has had multiple recent psychosocial stressors, including beginning college, starting a new job, and experiencing the events surrounding his parent's divorce. The patient appears emotionless and is difficult to acquire information from during the interview. He smiles at inappropriate times, and when asked what is humoring him, he looks down at the floor and says, “nothing.” According to the mother, the patient has had significant difficulty “expressing himself,” but he does mumble incoherent statements to himself repeatedly. She states she has never heard some of these words before. His mother further confirms that he has lost weight over the past two months and believes that this is due to his decreased appetite. Which of the following is the next best step in the management of this patient?

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A 47-year-old woman with a history of schizoaffective disorder, depressive type, is brought up to the psychiatry ward after receiving a haloperidol injection for severe agitation in the emergency department. As per reports, the patient has been non-compliant with her medications for the past two months. The patient is bizarre appearing and disheveled. She is found to be pacing the halls, mumbling incoherently to herself, and seems to be responding to internal stimuli. She becomes somewhat irritable when questioned, but is easily redirectable. Which of the following is the most appropriate choice of treatment for this patient?

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Psychosis - References


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