Which of the following describes the continuum approach to research in abnormal psychology?

Continuum (Minneap Minn). 2015 Jun; 21(3 Behavioral Neurology and Neuropsychiatry): 715–736.

Abstract

Purpose of Review:

Psychosis is a common and functionally disruptive symptom of many psychiatric, neurodevelopmental, neurologic, and medical conditions and an important target of evaluation and treatment in neurologic and psychiatric practice. The purpose of this review is to define psychosis, communicate recent changes to the classification of and criteria for primary psychotic disorders described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and summarize current evidence-based approaches to the evaluation and management of primary and secondary psychoses.

Recent Findings:

The DSM-5 classification of and criteria for primary psychotic disorders emphasize that these conditions occur along a spectrum, with schizoid (personality) disorder and schizophrenia defining its mild and severe ends, respectively. Psychosis is also identified as only one of several dimensions of neuropsychiatric disturbance in these disorders, with others encompassing abnormal psychomotor behaviors, negative symptoms, cognitive impairments, and emotional disturbances. This dimensional approach regards hallucinations and delusions as arising from neural systems subserving perception and information processing, thereby aligning the neurobiological framework used to describe and study such symptoms in primary psychotic disorders with those used to study psychosis associated with other neurologic conditions.

Summary:

This article provides practicing neurologists with updates on current approaches to the diagnosis, evaluation, and treatment of primary and secondary psychoses.

INTRODUCTION

Psychosis is a common and functionally disruptive symptom of many psychiatric, neurodevelopmental, neurologic, and medical conditions and an important target of evaluation and treatment in neurologic and psychiatric practice. This article defines psychosis, communicates recent changes to the classification of and criteria for primary psychotic disorders described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and summarizes current evidence-based approaches to the evaluation and management of primary and secondary psychoses. The definitions of psychosis used in the DSM-5 and International Classification of Diseases, Tenth Revision (ICD-10) are presented, and hallucinations, delusions, and delusional misidentification syndromes are defined and tabulated. The current classification, updated criteria, and approaches to the evaluation of schizophrenia spectrum and related psychotic disorders, as well as psychoses in neurologic conditions, are reviewed. Practical guidance on the evaluation and treatment of these conditions is drawn from practice guidelines promulgated by the professional societies and other international organizations, supplemented with findings published in more recent meta-analyses and systematic reviews.

Psychosis is the defining feature of schizophrenia spectrum disorders, a common but variable feature of mood and substance use disorders, and a relatively common feature of many developmental, acquired, and degenerative neurologic and medical conditions. Across these conditions, psychosis is both a contributor to disability and a barrier to productivity and participation.1–4 Psychosis is, therefore, an important target of evaluation and treatment among patients receiving care from neurologists and psychiatrists.

This article also defines psychosis and reviews the essential clinical features of primary psychotic disorders and psychoses secondary to neurologic conditions. The criteria for psychotic disorders included in the DSM-5,5 which have been revised substantially relative to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR),6 are a major focus of this review. The revised diagnostic criteria for secondary psychoses (those due to neurologic or medical conditions, substance use, and medications) also are reviewed briefly and the psychoses associated with common neurologic conditions tabulated. Finally, practical and evidence-based suggestions for the evaluation and treatment of primary and secondary psychotic disorders are presented.

DEFINING PSYCHOSIS

In early editions of the American Psychiatric Association’s (APA’s) Diagnostic and Statistical Manual of Mental Disorders (DSM),7 psychosis was defined broadly as “gross impairment in reality testing” or “loss of ego boundaries” that interferes with the capacity to meet the ordinary demands of life. This approach to defining psychosis emphasized the presence of functional limitations over the symptoms putatively responsible for them6 and too often rendered the distinction between psychotic and nonpsychotic mental disorders ambiguous. Concurrently, the International Classification of Diseases, Ninth Revision ([ICD-9], published in 1975) employed the then-traditional division between “neurosis” and ”psychosis” in its classification of mental disorders while deliberately making no attempt to define these terms.8 As a result, the category of psychotic disorders in the early editions of the DSM and in the ICD-9 were overly inclusive and, with respect to clinical, research, and epidemiologic endeavors, ultimately proved impracticable.6,8

In their current conceptualization of psychosis, both the APA5 and the World Health Organization8 define psychosis narrowly by requiring the presence of hallucinations (without insight into their pathologic nature), delusions, or both hallucinations without insight and delusions.6 In both of these current diagnostic classification systems, impaired reality testing remains central conceptually to psychosis. In contrast to earlier diagnostic classification systems, the current systems5,8 operationalize impaired reality testing by identifying the symptoms that provide evidence of such impairment. Delusions (ie, fixed false beliefs), by definition, are evidence of impaired reality testing: delusional beliefs are ones maintained steadfastly even in the face of evidence contradicting them incontrovertibly. Similarly, hallucinations (ie, perceptions occurring in the absence of corresponding external or somatic stimuli) are evidence of impaired reality when the individual experiencing them is unable to recognize the hallucinatory nature of such experiences. Both the current APA5 and the World Health Organization8 classification systems acknowledge that “formal thought disorder” (ie, disorganized thinking, including illogicality, tangentiality, perseveration, neologism, thought blocking, derailment, or some combination of these disturbances of thought) is one of several commonly co-occurring features of psychotic disorders. The DSM-55 allows formal thought disorder to supplant hallucinations and delusions in the diagnosis of a psychotic disorder when it is accompanied by grossly disorganized behavior, catatonia (for schizophrenia, schizophreniform, brief psychotic, and schizoaffective disorders) and/or negative symptoms (for schizophrenia, schizophreniform, and schizoaffective disorders but not brief psychotic disorder), alone or in combination.8 Since mildly disorganized speech is common and diagnostically nonspecific, the degree of thought disorder required to fulfill this DSM-5 criterion must be of severity sufficient to substantially impair effective communication.

For the purposes of this article, the term psychosis refers to the presence of delusions, hallucinations without insight, or both. These symptoms are clearly defined common features of psychosis in both psychiatric disorders and neurologic conditions. They are captured by informal and structured clinical assessments and are reasonably amenable to treatment.

Hallucinations

Hallucination is defined as a sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs. Hallucinations may occur with or without insight into their hallucinatory nature. The absence of insight into a hallucination defines it as a psychotic symptom, that is, a hallucination for which reality testing is impaired. Hallucinations without insight are contrasted with hallucinations that the individual recognizes as unreal. Examples of hallucinations with preserved insight include the visual hallucinations of migraine aura, sleep transition-related hypnagogic (while falling asleep) and hypnopompic (while waking) hallucinations, and the hallucinated hearing of one’s name being called that many psychiatrically and neurologically healthy individuals experience occasionally.

Schneider9 described auditory hallucinations involving hearing voices conversing with one another, offering running commentary on one’s actions, and “thought echoes” (hallucinations in which the patient hears his or her thoughts spoken aloud) as “first-rank” symptoms of schizophrenia. The first two of these types of auditory hallucinations have been regarded as so abnormal that their presence alone (in the absence of delusions or other thought, speech, and behavioral disturbances or negative symptoms) was sufficient to warrant a diagnosis of schizophrenia under the criteria of the DSM-IV-TR6 and its predecessors.

Hallucination is distinguished from illusion (misperception of an actual sensory stimulus) and the other disturbances of perception or experience described in Table 8-1.10 These perceptual phenomena occur in many neuropsychiatric conditions, including primary psychiatric disorders, neurologic disorders, medical illnesses, and substance intoxication and withdrawal states. Some of these perceptual phenomena (eg, illusions, hallucinations, synesthesia, derealization, depersonalization, autoscopy, déjà vu or déjà entendu, jamais vu or jamais entendu) are also reported by neuropsychiatrically healthy individuals. Their occurrence is not necessarily pathologic, especially if they occur with preserved insight, they are not associated with other disturbances of cognition, emotion, or behavior, and they do not compromise personal, social, or occupational function.

Table 8-1

Disturbances of Perception and Experience in the Differential Diagnosis of Hallucinationsa

Delusions

Delusions are fixed false beliefs; they are based on incorrect (false) inferences about reality external to, or about, oneself and maintained firmly (fixed) despite the presentation of evidence that obviously and incontrovertibly contradicts the belief. Table 8-2 defines and describes the types of delusions commonly occurring in individuals with primary and secondary psychotic disorders.10 These delusions are often divided into two types: ordinary and bizarre. Ordinary delusions derive from misinterpretation of everyday experiences and, as such, are understandable but not accepted by other members of the person’s culture or subculture (ie, are not articles of religious faith). For example, a patient who believes that an unknown group of conspirators is diverting his savings to a terrorist group despite being presented with evidence to the contrary (eg, bank statements) has an ordinary delusion (more specifically, an ordinary persecutory delusion). Bizarre delusions involve phenomena that are physically impossible or that most people in that person’s culture would regard as entirely implausible. The DSM-IV-TR provided as an example of bizarre delusion the belief that a stranger removed one’s internal organs and replaced them with another person’s organs without leaving any wounds or scars.6

Table 8-2

Delusions Observed Among Patients With Neuropsychiatric Disordersa

Schneider9 described specific types of bizarre delusions as “first-rank” symptoms of schizophrenia. (“First-rank” refers to symptoms that, when present, indicate the presence of a particular diagnosis [in the case of Schneiderian first-rank symptoms, the diagnosis of schizophrenia]). These include delusions of control, including thought control, as well as thought withdrawal and thought insertion. The presence of bizarre delusions, especially of these types, has long been regarded as so abnormal that their presence alone (in the absence of delusions or other thought, speech, and behavioral disturbances or negative symptoms) was sufficient to warrant a diagnosis of schizophrenia under DSM-IV-TR and its predecessors.

Delusions are contrasted with overvalued ideas, which are unreasonable beliefs or ideas that are held with strong, but not delusional, conviction. When a false belief involves a value judgment, it may be regarded as delusional only when the judgment made is so extreme that it is not credible. Delusions are distinct from confabulation, which refers to the automatic and nondeceitful fabrication of information, usually of an autobiographical or episodic nature, by a patient with concurrent declarative memory impairments and executive dysfunction.11 Confabulated information (even when fantastic in character) may be firmly believed in the moment that it is offered but is usually soon forgotten and, as such, is false but not fixed and, hence, not delusional.

Delusional misidentification syndromes. Delusional misidentification syndromes (Table 8-310) share the theme of doubles (ie, duplication of self, others, or the environment). They are associated with impairments in facial processing and are closely related to and sometimes co-occur with reduplicative paramnesia.12,13 Phenomenologically, delusional misidentification syndromes may be divided into two types: delusional hypoidentification (eg, Capgras syndrome) or delusional hyperidentification (eg, Frégoli, intermetamorphosis, subjective doubles syndromes). Although delusional misidentification syndromes occur commonly among patients with psychiatric illnesses, especially primary psychotic disorders, as many as 20% to 40% occur in the context of neurologic conditions affecting the right hemisphere.12,13 Accordingly, the presence of these types of delusions should prompt evaluation for potentially treatable or arrestable neurologic conditions.

Table 8-3

Examples of Delusional Misidentification and Other Delusions Involving a Belief That the Identity of a Person, Object, or Place Has Been Changed or Replaceda

PRIMARY PSYCHOTIC DISORDERS

A subset of the population with genetic, epigenetic, and developmental risk factors may, with sufficient exposure to risk-modifying social and environmental factors, be prone to developing persistent psychotic symptoms.14–16 This psychosis proneness-persistence model may explain, at least in part, the development of hallucinations and delusions across the broad range of psychiatric disorders with which they are associated. It also may yield insights into the risk factors for and mechanisms of psychosis associated with neurologic conditions. This model aligns well with the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, within which phenomena such as delusions and hallucinations are studied in relation to the operations of underlying neural systems across the conditions in which they occur, rather than in relation to the categorical psychiatric disorders with which they may be associated.17,18

In this light, it is not surprising that psychosis is listed as a feature of multiple psychiatric disorders presented in the DSM-5. Although psychosis is the defining feature of the schizophrenia spectrum disorders (ie, schizophrenia, schizoaffective disorder, delusional disorder, schizophreniform disorder, and brief psychotic disorder), it also occurs in some people with bipolar disorder during either a manic or depressive episode as well as in some individuals during a major depressive episode associated with major depressive disorder. In those conditions, the psychotic symptoms (usually delusions) may be thematically either congruent or incongruent with the prevailing mood. Psychotic symptoms (ie, hallucinations without insight, delusions) may develop during either intoxication or withdrawal from substances and, in some cases, may become chronic sequelae of prior substance use (substance-induced psychotic disorder). When individuals with obsessive-compulsive disorder lack insight into the pathologic nature of their obsessions, their obsessions are described as delusions. The psychosis proneness-persistence model and RDoC approach suggests that the presence of hallucinations or delusions reflects disturbances in the neural systems underlying these symptoms regardless of the categorical psychiatric or neurologic disorder with which they are associated.

A complete review of psychosis as it occurs in each of these conditions is beyond the scope of the present article. Readers are encouraged to review the relevant sections of the DSM-5 and to familiarize themselves with the current criteria for these conditions. To help keep readers up-to-date, major changes made to the criteria for psychotic disorders in the transition from the DSM-IV-TR to the DSM-5 are reviewed in this article.

Schizophrenia Spectrum Disorders

The DSM-5 marks a shift from the presentation of schizophrenia as the archetypal psychotic disorder to its consideration as one of several psychotic disorders existing on a spectrum of psychopathology. Disorders along the schizophrenia spectrum differ from one another by the type, number, complexity, severity, and duration of the psychotic symptoms and associated features that define them. Symptoms of schizophrenia spectrum disorders include hallucinations, delusions, disorganized thinking (formal thought disorder, usually inferred from an individual’s speech), grossly disorganized or abnormal motor behavior (including catatonia), and negative symptoms. The number, complexity, and duration of symptoms required for a given diagnosis increase with movement from the mild to the severe ends of the schizophrenia spectrum.

Consistent with this essentially dimensional approach to the evaluation of psychotic symptoms, the DSM-5 introduced the Clinician-Rated Dimensions of Psychosis Symptom Severity scale in Section III, “Emerging Measures and Models.”8,19 This scale is an eight-item measure that rates the severity of each symptom that defines the schizophrenia spectrum disorders (hallucinations, delusions, disorganized speech, abnormal psychomotor behavior, negative symptoms) as well as co-occurring cognitive, depressive, and manic symptoms during the week prior to assessment on a scale from 0 (not present) to 4 (present and severe). Assessment of this constellation of symptoms with these measures is described in the DSM-5 as useful for characterizing these conditions, predicting important aspects of the illness (eg, cognitive and neurobiological deficits), informing treatment planning and prognosis, and monitoring symptom severity over time. The severity of the disorders in this section of the DSM-5 may be assessed with this scale, which the APA has made freely available for clinical use (www.psychiatry.org/File%20Library/Practice/DSM/DSM-5/ClinicianRatedDimensionsOfPsychosisSymptomSeverity.pdf).19 The provision of this measure is coupled with the request that clinicians and researchers provide further data on the instrument’s usefulness in characterizing patient status and improving patient care by submitting feedback at www.dsm5.org/Pages/Feedback-Form.aspx. Given the emerging nature of this measure, the DSM-5 encourages, but does not require, using the Clinician-Rated Dimensions of Psychosis Symptom Severity scale to specify severity of illness in the schizophrenia spectrum disorders.

Schizotypal (personality) disorder. At the mild end of the schizophrenia spectrum disorders is schizotypal disorder (also known as schizotypal personality disorder). Schizotypal disorder is characterized by social and interpersonal deficits that reduce the capacity for, and produce marked discomfort with, close relationships. These deficits are often accompanied by unusual perceptual experiences (illusions) and cognitive distortions (ideas of reference, suspiciousness or paranoia, odd beliefs, or magical thinking that are held without delusional conviction) similar to, but less severe than, those experienced by people with schizophrenia. As noted by Chemerinski and colleagues,20 schizotypal disorder and schizophrenia feature cognitive, social, and attentional deficits based in neurodevelopmentally mediated temporal and prefrontal cortical pathology. These deficits are milder in people with schizotypal disorder than in those with schizophrenia, possibly as a result of preserved capacity in the schizotypal brain to recruit related brain regions and thereby compensate for dysfunctional areas. Additionally, people with schizotypal disorder appear to be less vulnerable to psychosis as a result of the preservation of protective factors against the psychotogenic effects of subcortical dopaminergic hyperactivity. Although the criteria for schizotypal disorder have not changed substantively between the DSM-IV-TR and DSM-5, the presentation of this condition as both a schizophrenia spectrum disorder and a personality disorder is a noteworthy change in its classification.

Delusional disorder. Delusional disorder encompasses a broader range of the spectrum of psychosis severity in the DSM-5 than in the prior edition of this manual. In both the DSM-IV-TR and DSM-5, this diagnosis requires the presence of one or more delusions lasting at least 1 month in the absence of prominent hallucinations (Case 8-1). If present, hallucinations must be related to the delusional theme (eg, tactile hallucinations of bugs on the skin in a patient with delusions of parasitosis). In the DSM-IV-TR, bizarre delusions exceeded the criteria for delusional disorder and were sufficient grounds for a diagnosis of schizophrenia (even in the absence of hallucinations, disorganized thought or behavior, catatonia, or negative symptoms).6 In the DSM-5, however, allowance of Schneiderian first-rank symptoms to suffice for the diagnosis of schizophrenia has been eliminated. As a result, the presence of either ordinary or bizarre delusions (or both) is now consistent with a diagnosis of delusional disorder, although the presence of bizarre content is used as a specifier in this diagnosis.

Brief psychotic disorder. This diagnosis is defined by the presence of delusions, hallucinations, formal thought disorder (ie, disorganized speech), or abnormal psychomotor behavior (grossly disorganized or catatonic behavior), not better explained by another mental disorder, substance use disorder, or medical condition, lasting at least 1 day but less than 1 month, with eventual full return to premorbid function. Negative symptoms are not among the diagnostic criteria for this condition. As in the DSM-IV-TR, current specifiers for brief psychotic disorder include the condition’s relationship to marked stressors (which, if present, define brief reactive psychosis) or postpartum onset (during pregnancy or within 4 weeks postpartum). The DSM-5 adds a specifier for the presence of catatonia, as well as a coding note directing the use of the additional 293.89 code (catatonia associated with brief psychotic disorder) to indicate this comorbidity.

Schizophreniform disorder. Schizophreniform disorder represents a point on the spectrum between brief psychotic disorder and schizophrenia. Analogous to changes made to the criteria for schizophrenia, this condition is defined by the presence of two or more psychotic and related symptoms (delusions, hallucinations, disorganized speech reflecting formal thought disorder, abnormal psychomotor behavior such as grossly disorganized or catatonic behavior, negative symptoms)—at least one of which must be delusions, hallucinations, or disorganized speech—lasting at least 1 month but less than 6 months. The DSM-5, in contrast to the DSM-IV-TR, permits making a provisional diagnosis of schizophreniform disorder when a diagnosis must be made before the end of this time period (without waiting for possible recovery). It also clarifies the exclusion of schizoaffective disorder, major depressive disorder, and bipolar disorder by specifying that no major depressive or manic symptoms may occur with active-phase psychotic symptoms or, if such symptoms have been present, that they have been present for a minority of the total active and residual phases of the illness. As with brief psychotic disorder, an additional specifier and related coding note have been added to indicate the presence of comorbid catatonia.

Schizophrenia. The DSM-5 includes substantive changes to the diagnostic criteria for schizophrenia. The core criteria continue to require the presence of two or more psychotic and related symptoms (delusions, hallucinations, disorganized speech reflecting formal thought disorder, abnormal psychomotor behavior such as grossly disorganized or catatonic behavior, negative symptoms)—at least one of which must be delusions, hallucinations, or disorganized speech—that have been present for at least 6 months (including 1 month, or less if treated successfully, of active psychotic and related symptoms). These symptoms also must be associated with impaired functioning in one or more major life areas such as self-care, work, interpersonal relations, or academics.

The DSM-IV-TR permitted diagnosing schizophrenia when first-rank delusions or auditory hallucinations occurred in the absence of other symptoms. However, first-rank symptoms are not specific to schizophrenia and may occur in manic and depressive episodes with psychotic features, temporal lobe epilepsy, dissociative identity disorder, and other psychiatric conditions.21 Accordingly, the DSM-5 eliminates the presence of first-rank hallucinations or delusions as grounds for reducing the number of symptoms required for the diagnosis of schizophrenia. This change is coordinated with the DSM-5 revised criteria for delusional disorder such that patients presenting only with bizarre delusions, and thereby failing to meet criteria for schizophrenia, can now be diagnosed with delusional disorder. As with schizophreniform disorder, clarification of the exclusion of schizoaffective disorder, major depressive disorder, and bipolar disorder is offered, and an additional specifier and related coding note have been added to indicate the presence of comorbid catatonia.

In contrast to prior editions of the DSM, schizophrenia subtypes have been eliminated in DSM-5. These subtypes (paranoid, disorganized, catatonic, undifferentiated, residual) were defined previously by the predominant symptom at the time of a given evaluation. However, the validity of these subtypes was controversial given their longitudinal instability, overlapping features, and failure to consistently predict outcomes.22 Recognizing these problems and the waning use of schizophrenia subtypes in clinical and research contexts,23 the DSM-5 eliminates schizophrenia subtyping in favor of characterizing the features of schizophrenia using the Clinician-Rated Dimensions of Psychosis Symptom Severity scale.

Schizoaffective disorder. Defining schizoaffective disorder has presented challenges to the psychiatric research community.24 Some investigators regard it as variant of schizophrenia in which mood symptoms are unusually prominent but not unusual in type. Others describe it as a mood disorder in which mood episode–related psychotic symptoms do not fully remit. Still others view it as the simple co-occurrence of two relatively common but etiologically distinct psychiatric illness types, schizophrenia and a mood disorder. The problem of schizoaffective disorder remains unresolved in the DSM-5, although criteria are revised in a manner that is likely to reduce the frequency with which it is diagnosed.

As in the DSM-IV-TR, the current diagnostic criteria for schizoaffective disorder require an uninterrupted period of illness during which a major mood episode occurs concurrently with a disturbance meeting Criterion A for schizophrenia (two or more of the following: delusions, hallucinations, disorganized speech reflecting formal thought disorder, abnormal psychomotor behavior, negative symptoms, at least one of which is delusions, hallucinations, or disorganized speech). Over the lifetime of the illness, delusions or hallucinations also must occur for at least 2 weeks in the absence of either a manic or depressive episode. This requirement of a 2-week (or longer) episode of psychosis in the absence of mood symptoms distinguishes schizoaffective disorder from either bipolar or depressive disorders with psychotic features, in which psychotic symptoms occur only during mood episodes. Course specifiers for bipolar or depressive subtypes of schizoaffective disorder and a new specifier for catatonic features are presented in the current criteria.

In contrast to the DSM-IV-TR, however, the DSM-5 requires the presence of symptoms meeting criteria for manic and/or depressive episodes for the majority (not merely a substantial portion) of the total duration of the illness. This criterion requires assessment of mood symptoms over the entire course of a psychotic illness rather than merely the current period of illness; if mood symptoms are present only for a relatively brief period (eg, during only 1 year of a 4-year psychotic illness), then a diagnosis of schizophrenia is made instead of a diagnosis of schizoaffective disorder. The information requirements needed to confidently establish a diagnosis of schizoaffective disorder necessitate a fully informed longitudinal perspective on the totality of a patient’s symptoms that often will not be arrived at easily, if at all, in many clinical practices.

Other specified schizophrenia and other psychotic disorders. The DSM-5 introduces this subcategory to provide for the diagnosis of four conditions involving psychotic symptoms that do not meet full criteria for any of the schizophrenia spectrum disorders but nonetheless are issues of clinical concern. Below are examples of clinical presentations to which the “other specified” designation applies.

• Persistent auditory hallucinations, denoting the persistent presence of auditory hallucinations occurring in the absence of other psychotic features.

• Delusions with significant overlapping mood episodes, which is most appropriately used when a patient otherwise meeting criteria for delusional disorder also experiences overlapping mood episodes for a substantial portion of the delusional disturbance.

• Attenuated psychosis syndrome, which describes a condition in which psychotic-like symptoms are present but are less severe and more transient than in schizophrenia, and for which insight is relatively maintained.

• Delusional symptoms in a partner of individual with delusional disorder (formerly named shared psychotic disorder, also known as folie a` deux), a rare condition in which delusions develop in an individual who is involved in a close relationship with an individual with prominent delusions. The previously unaffected partner’s delusions take on the content of the dominant partner’s delusions.

Unspecified schizophrenia spectrum and other psychotic disorder. The DSM-5 replaces “psychotic disorder not otherwise specified” with “unspecified schizophrenia spectrum and other psychotic disorder.” As in the DSM-IV-TR, this diagnosis applies to presentations in which functionally disabling or subjectively distressing symptoms characteristic of schizophrenia spectrum and other psychotic disorders predominate but do not meet full criteria for another condition in this category. It also applies to presentations about which insufficient information exists to make a more specific diagnosis. New in the DSM-5 is the instruction to use the “unspecified schizophrenia spectrum and other psychotic disorder” diagnosis in circumstances in which the clinician chooses not to specify the reason that the criteria are not met for another schizophrenia spectrum or psychotic disorder. The practical usefulness of this diagnosis is not established.

Case 8-1

A 19-year-old previously healthy man was brought in by his parents for evaluation of paranoid ideation. The parents reported that the patient had always been a loner, worked from home as a computer programmer, and spent most of his leisure time in his room browsing the Internet, watching detective shows on television, and listening to a police scanner. A little over 1 month prior to presentation, he began refusing to leave his room, keeping the curtains drawn constantly, and taking copious notes about the comings and goings of his neighbors. After a week of these new behaviors, his parents asked him to explain the changes to his routine. He told them that a black sedan had begun parking across the street from their home each evening and departing early each morning, leading him to conclude that he was the subject of surveillance by the Federal Bureau of Investigation. When his parents informed him that the car was recently purchased by their longtime next-door neighbor and family acquaintance, he then concluded that the neighbor was the federal agent surveilling him. Despite repeated attempts to convince him otherwise, including a conversation with the neighbor, who explained his recent purchase of a luxury car to ease his long daily commutes, the patient’s paranoid beliefs remained unchanged. Physical and neurologic examinations were normal, and mental status examination was remarkable only for the patient’s delusion. Serum laboratory studies, urine toxicology, and MRI of the brain were normal.

Comment. The patient presented with a nonbizarre delusion as his sole symptom. The presence of this type of delusion for more than 1 month in the absence of prominent hallucinations, when not better explained by a known psychotic disorder or mood disorder with psychotic features and not attributable to the physiologic effects of a substance or another medical condition, is consistent with a provisional diagnosis of delusional disorder (297.1), current severity of delusions: 4 (present and severe).

SECONDARY PSYCHOTIC DISORDERS

The DSM-5 notes the common co-occurrence of psychotic symptoms (ie, hallucinations without insight, delusions) in people with neurocognitive disorders due to Alzheimer disease, Parkinson disease, diffuse Lewy body disease, frontotemporal lobar degeneration, Huntington disease, prion disease, cerebrovascular disease, traumatic brain injury, HIV, and substances/medications, among others. When psychotic symptoms develop in association with cognitive impairments due to these conditions, the DSM-5 suggests qualifying the neurocognitive disorder diagnosis with the specifier “with behavioral disturbance (psychosis)” rather than offering a concurrent schizophrenia spectrum disorder diagnosis. When hallucinations or delusions predominate the clinical presentation, are not better explained by another mental disorder, are not merely symptoms of a delirium, are functionally impairing or distressing, and when there is evidence that their occurrence is pathophysiologically linked to either a neurologic or medical condition or substance abuse or medication, then a diagnosis of “psychotic disorder due to another medical condition” or “substance/medication-induced psychotic disorder,” respectively, may be made.

A detailed review of the clinical features of psychosis associated with neurologic conditions is beyond the scope of this review, as the literature describing the phenomenology, epidemiology, and putative neurobiology of hallucinations and delusions associated with neurologic disorders has expanded rapidly over the last 2 decades. As a brief review, Table 8-425,26 summarizes and comments on the psychotic symptoms associated with more than a dozen neurologic conditions and their possible anatomic correlates.

Table 8-4

Examples of Neurologic Conditions Associated With Psychosisa,b

EVALUATION AND MANAGEMENT

Useful direction for the evaluation and management of patients with schizophrenia spectrum and related disorders,27 as well as other psychiatric and neurologic conditions in which psychotic symptoms developed, is found in the APA Clinical Practice Guidelines (psychiatryonline.org/guidelines).28 The American Academy of Neurology (AAN) practice parameters and evidence-based guidelines (www.aan.com/Guidelines) may also be useful for clinicians evaluating and managing patients with secondary psychoses.29 More recent guidelines on these topics, including those promulgated in 2013 by the Scottish Intercollegiate Guidelines Network (SIGN),30 are freely available from the National Guideline Clearinghouse (www.guideline.gov).31 With regard to the application of guidelines to clinical decision making, the Agency for Healthcare Research and Quality recommends using guidelines published within 5 years of the time at which they are used (www.guideline.gov/about/inclusion-criteria.aspx). Thus, clinicians evaluating and developing treatment plans for patients with primary or secondary psychoses are encouraged to access guidelines in the National Guideline Clearinghouse repository and similar resources,32–34 to integrate the guidance they offer with that presented in relevant professional society guidelines (especially when those guidelines are more than 5 years old), and to supplement all guidelines with findings presented in subsequently published meta-analyses and systematic reviews.

Evaluation

Central to all of the presently available guidelines on the evaluation and management of patients with psychosis is the need to identify the cause of psychotic symptoms (in order of priority: delirium, including delirium due to substance intoxication/withdrawal; secondary psychoses of neurologic, medical, and substance use disorders; mood disorders with psychotic features; schizophrenia spectrum disorders; and other psychotic disorders) through comprehensive neuropsychiatric assessment. Patients should be involved in psychiatric, neurologic, and general medical history taking to the extent that their clinical status allows, and, whenever possible, collateral and corroborative history should be obtained from family members or others knowledgeable about the patient and from medical records. Evaluation for potentially causative or contributory medications (eg, prodopaminergic or anticholinergic agents) and substance use disorders is essential.27 Vital signs and body mass index measurements, physical, neurologic, and mental status examinations, and evaluation for substance use should be performed routinely.27 When the history or examination findings suggest that psychotic symptoms may be the product of a subacute or chronic neurologic condition, neuroimaging (CT or MRI) and EEG may be diagnostically informative.27 When the history or examination findings suggest the presence of either delirium or another nonpsychiatric cause of psychotic symptoms, relevant serum, urine, and CSF studies should be performed.

With regard to evaluation of the psychosis specifically, patient interview and observation using the Brief Psychiatric Rating Scale (BPRS)35 or Positive and Negative Syndrome Scale (PANSS)36 as well as interview of a knowledgeable informant using one of the several versions of the Neuropsychiatric Inventory (NPI)37 (npitest.net), may be useful. Evaluation for manic and depressive episodes (current and lifetime) anchored to DSM-5 criteria should be performed, as strict adherence to these criteria is required to distinguish between schizophrenia mood disorders with psychotic features and schizoaffective disorder. The DMS-5 encourages use of the Clinician-Rated Dimensions of Psychosis Symptom Severity scale to rate the severity of both manic and depressive symptoms associated with schizophrenia spectrum and other psychotic disorders.19 Cognitive and functional assessments, to the extent the patient is able to participate effectively in them, also guide diagnosis and treatment planning. The DSM-5 directs clinicians to interpret measures using normative data for age and for socioeconomic status; as few measures provide socioeconomic status–adjusted norms, normative data for education may serve as the closest proxy for this adjustment. The Clinician-Rated Dimensions of Psychosis Symptom Severity scale rates the severity of cognitive impairment in increments of standard deviations (SD) below the mean for age and socioeconomic status (0: no impairment; 1: equivocal, between 0 and 0.5 SD; 2: mild, −0.5 to −1 SD; 3: moderate, −1 to −2 SD; 4: severe, less than −2 SD).19 Neuropsychological and occupational therapy consultations contribute usefully to cognitive and functional assessments and should be performed when feasible.

Treatment

Systematic reviews and meta-analyses demonstrate that typical (first-generation) and atypical (second-generation) antipsychotics are similar with respect to their beneficial effects on the frequency and severity of hallucinations and delusions.38,39 Clozapine is particularly effective in treatment-resistant populations and reduces suicide risk.39,40 Among patients with schizophrenia, atypical antipsychotics improve cognition41 and life satisfaction42 and may modestly contribute to improvements in functional status.43 Meta-analyses suggest that repetitive transcranial magnetic stimulation (rTMS) over the left temporoparietal region (in the area of T3-P3 in the International 10-20 System of Electrode Placement) is an effective treatment for the auditory verbal hallucinations that are refractory to treatment with antipsychotics.44 However, rTMS does not appear to be an effective treatment for other symptoms of schizophrenia.45

Acetylcholinesterase inhibitors, adjunctively or alternatively, may reduce psychosis in patients with Alzheimer disease,46 Parkinson disease dementia,47 diffuse Lewy body disease,48 and, to a lesser extent, schizophrenia and related conditions.49 However, antipsychotics remain commonly used to treat psychotic symptoms associated with neurologic disorders. Evidence of benefit from antipsychotic treatment of psychotic symptoms is mixed in patients with psychosis associated with Alzheimer disease,50,51 modest in Parkinson disease (for which clozapine and quetiapine are the preferred agents for psychosis that persists despite stepwise reductions in prodopaminergic medications),52 and limited for most other neurologic conditions. While acknowledging the limits of the evidence base for the treatment of psychosis associated with neurologic conditions, individual patients experiencing secondary psychosis may benefit, nonetheless, from judicious administration of antipsychotic medications, especially when other medications and nonpharmacologic interventions do not provide adequate relief from psychotic symptoms.53,54

Whether used to treat primary or secondary psychoses, antipsychotic treatment–related pretreatment evaluation of weight; metabolic status; cardiac, sexual, and neurologic (especially motor) function; and hematologic health as well as periodic monitoring for changes in these areas during treatment is recommended.27 The specific risks and parameters requiring monitoring differ between antipsychotics.38,55 Readers are encouraged to review the manufacturer’s product information for any specific medication prescribed as well as the recommendations on antipsychotic medication safety monitoring offered in the report of the Mount Sinai Conference on the Pharmacotherapy of Schizophrenia,56 and by the 2013 Scottish Intercollegiate Guidelines Network (SIGN).30 Among elderly patients with dementia and psychosis, the benefits of antipsychotic treatment must be balanced against the risk of serious adverse events. Informed consent requires acknowledgement of the 1.5 to 1.8 times increased mortality associated with antipsychotic treatment in elderly patients with dementia, the risk of which appears similar for both the typical and atypical antipsychotics54 (www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124830.htm).57

Psychosocial interventions also are essential elements of the treatment for patients with primary and secondary psychoses, especially during the stable phase of illness.27 These interventions include patient and family education, cognitive behaviorally oriented therapies, family interventions, assertive community treatment, social skills training, and supported employment. Additional nonpharmacologic interventions that may reduce contributors to psychotic symptoms, especially among patients with dementia-associated psychosis, include improving sensory function (eg, hearing aids, eyeglasses), identifying environmental antecedents to perceptual or cognitive misinterpretations, and stimulus controls that circumvent misinterpretations. Caregiver and family support also should be provided concurrently with patient-oriented therapies.58

CONCLUSION

Psychosis is a common symptom of many psychiatric, neurodevelopmental, neurologic, and medical conditions and is an important target of evaluation and treatment in neurologic and psychiatric practice. The DSM-5 classification of and criteria for primary psychotic disorders emphasize that these conditions occur along a spectrum, with schizoid (personality) disorder and schizophrenia defining its mild and severe ends, respectively. Psychosis is also identified as only one of several dimensions of neuropsychiatric disturbance in these disorders, with others encompassing abnormal psychomotor behaviors, negative symptoms, cognitive impairments, and emotional disturbances. This dimensional approach regards hallucinations and delusions as arising from neural systems subserving perception and information processing, thereby aligning the neurobiological framework used to describe and study such symptoms in primary psychotic disorders with those used to study psychosis associated with other neurologic conditions.

Comprehensive neuropsychiatric assessment is a prerequisite to the treatment of psychotic symptoms, and it prioritizes identification of medical, substance-related, and neurologic causes of psychosis over their attribution to psychiatric conditions. The use of structured clinical interviews of patients and knowledgeable informants to clarify the character of psychosis and associated symptoms is recommended in guidelines promulgated by the APA and similar professional societies. Data yielded by such interviews establishes a baseline for monitoring disease progression and against which the effects of treatment can be compared. Those treatments include pharmacotherapies and psychosocial interventions, the specific elements of which should follow up-to-date guidelines and findings presented in published meta-analyses and systematic reviews.

KEY POINTS

• The American Psychiatric Association and the World Health Organization emphasize the presence of hallucinations without insight or delusions in their current definitions of psychosis.

• Hallucination is defined as a sensory perception in the absence of a corresponding external or somatic stimulus and described according to the sensory domain in which it occurs.

• Hallucinations may occur with or without insight into their hallucinatory nature. The absence of insight into a hallucination defines it as a psychotic symptom, that is, a hallucination for which reality testing is impaired.

• Delusions are fixed false beliefs; they are based on incorrect (false) inferences about reality external to, or about, oneself and maintained firmly (fixed) despite the presentation of evidence that obviously and incontrovertibly contradicts the belief.

• Delusions are distinct from confabulation, which refers to the automatic and nondeceitful fabrication of information, usually of an autobiographic or episodic nature, by a patient with concurrent declarative memory impairments and executive dysfunction.

• Although delusional misidentification syndromes occur commonly among patients with psychiatric illnesses, especially primary psychotic disorders, as many as 20% to 40% occur in the context of neurologic conditions affecting the right hemisphere. Accordingly, the presence of these types of delusions should prompt evaluation for potentially treatable or arrestable neurologic conditions.

• The psychosis proneness-persistence model and Research Domain Criteria approach suggests that the presence of hallucinations or delusions reflects disturbances in the neural systems underlying these symptoms regardless of the categorical psychiatric disorder with which they are associated.

• Disorders along the schizophrenia spectrum differ from one another by the type, number, complexity, severity and duration of the psychotic symptoms and associated features that define them.

• Although the criteria for schizotypal disorder have not changed substantively between the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the presentation of this condition as both a schizophrenia spectrum disorder and a personality disorder is a noteworthy change in its classification.

• The DSM-5 eliminates the presence of first-rank hallucinations or delusions as grounds for reducing the number of symptoms required for the diagnosis of schizophrenia.

• In contrast to prior editions of the DSM, schizophrenia subtypes have been eliminated in the DSM-5.

• The DSM-5 eliminates schizophrenia subtyping in favor of characterizing the features of schizophrenia using the Clinician-Rated Dimensions of Psychosis Symptom Severity scale.

• New in the DSM-5 is the instruction to use the “unspecified schizophrenia spectrum and other psychotic disorder” diagnosis in circumstances in which the clinician chooses not to specify the reason that the criteria are not met for another schizophrenia spectrum or psychotic disorder.

• When evaluating and developing treatment plans for patients with primary or secondary psychoses, clinicians are encouraged to access guidelines in the National Guideline Clearinghouse repository and similar resources to integrate the guidance they offer with that presented in relevant professional societies’ guidelines and to supplement all guidelines with findings presented in subsequently published meta-analyses and systematic reviews.

• The DSM-5 directs clinicians to interpret measures using normative data for age and for socioeconomic status; as few measures provide socioeconomic status–adjusted norms, normative data for education may serve as the closest proxy for this adjustment.

• Systematic reviews and meta-analyses demonstrate that typical (first-generation) and atypical (second-generation) antipsychotics are similar with respect to their beneficial effects on the frequency and severity of hallucinations and delusions.

• Meta-analyses suggest that repetitive transcranial magnetic stimulation over the left temporoparietal region (in the area of T3-P3 in the International 10-20 System of Electrode Placement) is an effective treatment for the auditory verbal hallucinations that are refractory to treatment with antipsychotics.

• Acetylcholinesterase inhibitors, adjunctively or alternatively, may reduce psychosis in patients with Alzheimer disease, Parkinson disease dementia, diffuse Lewy body disease, and, to a lesser extent, schizophrenia and related conditions.

• Evidence of benefit from antipsychotic treatment of psychotic symptoms is mixed in patients with psychosis associated with Alzheimer disease, modest in Parkinson disease (for which clozapine and quetiapine are the preferred agents for psychosis that persists despite stepwise reductions in prodopaminergic medications), and limited for most other neurologic conditions.

• While acknowledging the limits of the evidence base for the treatment of psychosis associated with neurologic conditions, individual patients experiencing secondary psychosis may benefit, nonetheless, from judicious administration of antipsychotic medications, especially when other medications and nonpharmacologic interventions do not provide adequate relief from psychotic symptoms.

• Among elderly patients with dementia and psychosis, the benefits of antipsychotic treatment must be balanced against the risk of serious adverse events and discussion of both must be included in the informed consent process prior to initiating treatment with antipsychotic medications.

• Readers are encouraged to review the manufacturer’s product information for any specific medication prescribed as well as the recommendations on antipsychotic medication safety monitoring offered in the report of the Mount Sinai Conference on the Pharmacotherapy of Schizophrenia and by the 2013 Scottish Intercollegiate Guidelines Network.

• Psychosocial interventions also are essential elements of the treatment for patients with primary and secondary psychoses, especially during the stable phase of illness.

ACKNOWLEDGMENTS

This work was supported in part by the NIH grant NIMH R01 MH081920-02 and the Beth K. and Stuart Yudofsky Chair in Brain Injury Medicine at the Baylor College of Medicine.

USEFUL WEBSITES

American Psychiatric Association. The American Psychiatric Association (APA) has developed the Clinician-Rated Dimensions of Psychosis Symptom Severity scale, an eight-item measure that rates the severity of each symptom that defines the schizophrenia spectrum disorders as well as co-occurring cognitive, depressive, and manic symptoms during the week prior to assessment.

www.psychiatry.org/File%20Library/Practice/DSM/DSM-5/ClinicianRatedDimensionsOfPsychosisSymptomSeverity.pdf

The APA offers the Clinician-Rated Dimensions of Psychosis Symptom Severity scale without cost for clinical use, but requests that clinicians and researchers provide data on the instrument’s usefulness by submitting feedback at the website below.

dsm5.org/Pages/Feedback-Form.aspx

The APA also offers practice guidelines that provide evidence-based recommendations for the assessment and treatment of psychiatric disorders.

psychiatryonline.org/guidelines

Agency for Healthcare Research and Quality. The Agency for Healthcare Research and Quality maintains the National Guideline Clearinghouse website, a public resource for evidence-based clinical practice guidelines.

www.guideline.gov

Neuropsychiatric Inventory (NPI). The NPI screens for multiple types of dementia.

npitest.net

The Mount Sinai Conference on the Pharmacotherapy of Schizophrenia. This report provides guidance on the prescription and monitoring of antipsychotic medications, and it is available as a free full text download from Oxford Journals.

schizophreniabulletin.oxfordjournals.org/content/28/1/5.long

The Scottish Intercollegiate Guidelines Network (SIGN). SIGN 131, Management of Schizophrenia, provides a current set of guidelines on the evaluation and treatment of schizophrenia spectrum disorders as well as patient and family education materials.

www.sign.ac.uk/guidelines/fulltext/131/

REFERENCES

1. Morgan C, Lappin J, Heslin M, et al. Reappraising the long-term course and outcome of psychotic disorders: the AESOP-10 study. Psychol Med 2014; 44 (13): 2713– 2726. doi:10.1017/S0033291714000282. [PMC free article] [PubMed] [Google Scholar]

2. Rabinowitz J, Berardo CG, Bugarski-Kirola D, Marder S. Association of prominent positive and prominent negative symptoms and functional health, well-being, healthcare-related quality of life and family burden: a CATIE analysis. Schizophr Res 2013; 150 (2–3): 339– 342. doi:10.1016/j.schres.2013.07.014. [PubMed] [Google Scholar]

3. Vilalta-Franch J, Lopez-Pousa S, Calvo-Perxas L, Garre-Olmo J. Psychosis of Alzheimer disease: prevalence, incidence, persistence, risk factors, and mortality. Am J Geriatr Psychiatry 2013; 21 (11): 1135– 1143. doi:10.1016/j.jagp.2013.01.051. [PubMed] [Google Scholar]

4. Forsaa EB, Larsen JP, Wentzel-Larsen T, et al. A 12-year population-based study of psychosis in Parkinson disease. Arch Neurol 2010; 67 (8): 996– 1001. doi:10.1001/archneurol.2010.166. [PubMed] [Google Scholar]

5. American Psychiatric Association DSM-5 Task Force. Diagnostic and statistical manual of mental disorders, 5th Edition (DSM-5). Washington, DC: American Psychiatric Association, 2013. [Google Scholar]

6. American Psychiatric Association Task Force on DSM-IV. Diagnostic and statistical manual of mental disorders, 4th edition text revision (DSM-IV-TR). Washington, DC: American Psychiatric Association, 2000. [Google Scholar]

7. American Psychiatric Association Committee on Nomenclature and Statistics. Diagnostic and statistical manual of mental disorders, 2nd edition (DSM-II). Arlington: American Psychiatric Association, 1968. [Google Scholar]

8. World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva: World Health Organization, 1992. [Google Scholar]

9. Schneider K. Clinical psychopathology. New York: Grune & Stratton, 1959. [Google Scholar]

10. Arciniegas DB. Mental status examination. In: Arciniegas DB, Anderson CA, Filley CM, eds. Behavioral Neurology and Neuropsychiatry. Cambridge, England: Cambridge University Press; 2013: 344– 393. [Google Scholar]

11. Bonhoeffer K. Die akuten Geisteskrankheiten der Gewohnheitstrinker. Jena: G. Fischer, 1901. [Google Scholar]

12. Edelstyn NM, Oyebode F. A review of the phenomenology and cognitive neuropsychological origins of the Capgras syndrome. Int J Geriatr Psychiatry 1999; 14 (1): 48– 59. doi:10.1002/(SICI)1099-1166(199901)14:1<48::AID-GPS891>3.0.CO;2-0. [PubMed] [Google Scholar]

13. Christodoulou GN, Margariti M, Kontaxakis VP, Christodoulou NG. The delusional misidentification syndromes: strange, fascinating, and instructive. Curr Psychiatry Rep 2009; 11 (3): 185– 189. doi:10.1007/s11920-009-0029-6. [PubMed] [Google Scholar]

14. Arnedo J, Svrakic DM, Del Val C, et al. Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. Am J Psychiatry 2014. doi:10.1176/appi.ajp.2014.14040435. [Epub ahead of print]. [PubMed] [Google Scholar]

15. Linscott RJ, van Os J. An updated and conservative systematic review and meta-analysis of epidemiological evidence on psychotic experiences in children and adults: on the pathway from proneness to persistence to dimensional expression across mental disorders. Psychol Med 2013; 43 (6): 1133– 1149. doi:10.1017/S0033291712001626. [PubMed] [Google Scholar]

16. Morgan VA, Valuri GM, Croft ML, et al. Cohort profile: pathways of risk from conception to disease: the Western Australian schizophrenia high-risk e-Cohort. Int J Epidemiol 2011; 40 (6): 1477– 1485. doi:10.1093/ije/dyq167. [PubMed] [Google Scholar]

17. Insel T, Cuthbert B, Garvey M, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 2010; 167 (7): 748– 751. doi:10.1176/appi.ajp.2010.09091379. [PubMed] [Google Scholar]

18. Ford JM, Morris SE, Hoffman RE, et al. Studying hallucinations within the NIMH RDoC framework. Schizophr Bull 2014; 40 (suppl 4): S295– S304. doi:10.1093/schbul/sbu011. [PMC free article] [PubMed] [Google Scholar]

20. Chemerinski E, Triebwasser J, Roussos P, Siever LJ. Schizotypal personality disorder. J Pers Disord 2013; 27 (5): 652– 679. doi:10.1521/pedi_2012_26_053. [PubMed] [Google Scholar]

21. Saddichha S, Kumar R, Sur S, Sinha BN. First rank symptoms: concepts and diagnostic utility. Afr J Psychiatry (Johannesbg) 2010; 13 (4): 263– 266. doi:10.4314/ajpsy.v13i4.61874. [PubMed] [Google Scholar]

22. Tandon R, Gaebel W, Barch DM, et al. Definition and description of schizophrenia in the DSM-5. Schizophr Res 2013; 150 (1): 3– 10. doi:10.1016/j.schres.2013.05.028. [PubMed] [Google Scholar]

23. Braff DL, Ryan J, Rissling AJ, Carpenter WT. Lack of use in the literature from the last 20 years supports dropping traditional schizophrenia subtypes from DSM-5 and ICD-11. Schizophr Bull 2013; 39 (4): 751– 753. doi:10.1093/schbul/sbt068. [PMC free article] [PubMed] [Google Scholar]

24. Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat 2008; 4 (6): 1089– 1109. [PMC free article] [PubMed] [Google Scholar]

25. McAllister TW, Arciniegas DB. Pharmacotherapy of behavioral disturbances. In: Arciniegas DB, Anderson CA, Filley CM, eds. Behavioral Neurology and Neuropsychiatry. Cambridge, England: Cambridge University Press; 2013: 566– 586. [Google Scholar]

26. Rosenfeld MR, Titulaer MJ, Dalmau J. Paraneoplastic syndromes and autoimmune encephalitis: five new things. Neurol Clin Pract 2012; 2 (3): 215– 223. [PMC free article] [PubMed] [Google Scholar]

27. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, 2nd ed Arlington: American Psychiatric Association, 2004. [PubMed] [Google Scholar]

29. Clinical practice guidelines. American Academy of Neurology. www.aan.com/Guidelines. Accessed April 9, 2015.

31. National Guideline Clearinghouse. Agency for Healthcare Research and Quality. www.guideline.gov. Accessed April 9, 2015. [PubMed]

32. Stahl SM, Morrissette DA, Citrome L, et al. “Meta-guidelines” for the management of patients with schizophrenia. CNS Spectr 2013; 18 (3): 150– 162. doi:10.1017/S109285291300014X. [PubMed] [Google Scholar]

33. Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Schizophrenia, part 1: update 2012 on the acute treatment of schizophrenia and the management of treatment resistance. World J Biol Psychiatry 2012; 13 (5): 318– 378. doi:10.3109/15622975.2012.696143. [PubMed] [Google Scholar]

34. Hasan A, Falkai P, Wobrock T, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of schizophrenia, part 2: update 2012 on the long-term treatment of schizophrenia and management of antipsychotic-induced side effects. World J Biol Psychiatry 2013; 14 (1): 2– 44. doi:10.3109/15622975.2012.739708. [PubMed] [Google Scholar]

35. Overall JE, Gorham DR. The brief psychiatric rating scale. Psychol Rep 1962; 10: 799– 812. [Google Scholar]

36. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987; 13 (2): 261– 276. [PubMed] [Google Scholar]

37. Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994; 44 (12): 2308– 2314. doi:10.1212/WNL.44.12.2308. [PubMed] [Google Scholar]

38. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet 2013; 382 (9896): 951– 962. doi:10.1016/S0140-6736(13)60733-3. [PubMed] [Google Scholar]

39. Foussias G, Remington G. Antipsychotics and schizophrenia: from efficacy and effectiveness to clinical decision-making. Can J Psychiatry 2010; 55 (3): 117– 125. [PubMed] [Google Scholar]

40. Saunders KE, Hawton K. The role of psychopharmacology in suicide prevention. Epidemiol Psichiatr Soc 2009; 18 (3): 172– 178. doi:10.1017/S1121189X00000427. [PubMed] [Google Scholar]

41. Desamericq G, Schurhoff F, Meary A, et al. Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol 2014; 70 (2): 127– 134. doi:10.1007/s00228-013-1600-y. [PubMed] [Google Scholar]

42. Fervaha G, Agid O, Takeuchi H, et al. Effect of antipsychotic medication on overall life satisfaction among individuals with chronic schizophrenia: findings from the NIMH CATIE study. Eur Neuropsychopharmacol 2014; 24 (7): 1078– 1085. doi:10.1016/j.euroneuro.2014.03.001. [PubMed] [Google Scholar]

43. Percudani M, Barbui C, Tansella M. Effect of second-generation antipsychotics on employment and productivity in individuals with schizophrenia: an economic perspective. Pharmacoeconomics 2004; 22 (11): 701– 718. doi:10.2165/00019053-200422110-00002. [PubMed] [Google Scholar]

44. Slotema CW, Blom JD, van Lutterveld R, et al. Review of the efficacy of transcranial magnetic stimulation for auditory verbal hallucinations. Biol Psychiatry 2014; 76 (2): 101– 110. doi:10.1016/j.biopsych.2013.09.038. [PubMed] [Google Scholar]

45. Slotema CW, Blom JD, Hoek HW, Sommer IE. Should we expand the toolbox of psychiatric treatment methods to include Repetitive Transcranial Magnetic Stimulation (rTMS)? A meta-analysis of the efficacy of rTMS in psychiatric disorders. J Clin Psychiatry 2010; 71 (7): 873– 884. doi:10.4088/JCP.08m04872gre. [PubMed] [Google Scholar]

46. Pinto T, Lanctot KL, Herrmann N. Revisiting the cholinergic hypothesis of behavioral and psychological symptoms in dementia of the Alzheimer’s type. Ageing Res Rev 2011; 10 (4): 404– 412. doi:10.1016/j.arr.2011.01.003. [PubMed] [Google Scholar]

47. Wood LD, Neumiller JJ, Setter SM, Dobbins EK. Clinical review of treatment options for select nonmotor symptoms of Parkinson’s disease. Am J Geriatr Pharmacother 2010; 8 (4): 294– 315. doi:10.1016/j.amjopharm.2010.08.002. [PubMed] [Google Scholar]

48. Ballard C, Aarsland D, Francis P, Corbett A. Neuropsychiatric symptoms in patients with dementias associated with cortical Lewy bodies: pathophysiology, clinical features, and pharmacological management. Drugs Aging 2013; 30 (8): 603– 611. doi:10.1007/s40266-013-0092-x. [PubMed] [Google Scholar]

49. Singh J, Kour K, Jayaram MB. Acetylcholinesterase inhibitors for schizophrenia. Cochrane Database Syst Rev 2012; 1: CD007967 doi:10.1002/14651858.CD007967.pub2. [PMC free article] [PubMed] [Google Scholar]

50. Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry 2008; 165 (7): 844– 854. doi:10.1176/appi.ajp.2008.07111779. [PMC free article] [PubMed] [Google Scholar]

51. Gentile S. Second-generation antipsychotics in dementia: beyond safety concerns. A clinical, systematic review of efficacy data from randomised controlled trials. Psychopharmacology (Berl) 2010; 212 (2): 119– 129. doi:10.1007/s00213-010-1939-z. [PubMed] [Google Scholar]

52. Miyasaki JM, Shannon K, Voon V, et al. Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 66 (7): 996– 1002. [PubMed] [Google Scholar]

53. Ballard C, Creese B, Corbett A, Aarsland D. Atypical antipsychotics for the treatment of behavioral and psychological symptoms in dementia, with a particular focus on longer term outcomes and mortality. Expert Opin Drug Saf 2011; 10 (1): 35– 43. doi:10.1517/14740338.2010.506711. [PubMed] [Google Scholar]

54. Mittal V, Kurup L, Williamson D, et al. Risk of cerebrovascular adverse events and death in elderly patients with dementia when treated with antipsychotic medications: a literature review of evidence. Am J Alzheimers Dis Other Demen 2011; 26 (1): 10– 28. doi:10.1177/1533317510390351. [PubMed] [Google Scholar]

55. Zheng L, Mack WJ, Dagerman KS, et al. Metabolic changes associated with second-generation antipsychotic use in Alzheimer’s disease patients: the CATIE-AD study. Am J Psychiatry 2009; 166 (5): 583– 590. doi:10.1176/appi.ajp.2008.08081218. [PMC free article] [PubMed] [Google Scholar]

56. Marder SR, Essock SM, Miller AL, et al. The Mount Sinai conference on the pharmacotherapy of schizophrenia. Schizophr Bull 2002; 28 (1): 5– 16. [PubMed] [Google Scholar]

58. Herrmann N, Gauthier S. Diagnosis and treatment of dementia: 6. Management of severe Alzheimer disease. CMAJ 2008; 179 (12): 1279– 1287. doi:10.1503/cmaj.070804. [PMC free article] [PubMed] [Google Scholar]

Articles from Continuum : Lifelong Learning in Neurology are provided here courtesy of American Academy of Neurology