Midterms: Lesson 4 - Depressive Disorder Criterias

Diagnostic Criteria: Disruptive Mood Dysregulation Disorder

1. Severe recurrent temper outbursts manifested verbally (e.g., verbal rages) and/or behaviorally (e.g., physical aggression toward people or property) that are grossly out of proportion in intensity or duration to the situation or provocation.

2. The temper outbursts are inconsistent with developmental level.

3. The temper outbursts occur, on average, three or more times per week.

4. The mood between temper outbursts is persistently irritable or angry most of the day, nearly every day, and is observable by others (e.g., parents, teachers, peers).

5. Criteria A–D have been present for 12 or more months. Throughout that time, the individual has not had a period lasting 3 or more consecutive months without all of the symptoms in Criteria A–D.

6. Criteria A and D are present in at least two of three settings (i.e., at home, at school, with peers) and are severe in at least one of these.

7. The diagnosis should not be made for the first time before age 6 years or after age 18 years.

8. By history or observation, the age at onset of Criteria A–E is before 10 years.

9. There has never been a distinct period lasting more than 1 day during which the full symptom criteria, except duration, for a manic or hypomanic episode have been met.

   Note: Developmentally appropriate mood elevation, such as occurs in the context of a highly positive event or its anticipation, should not be considered as a symptom of mania or hypomania.

10. The behaviors do not occur exclusively during an episode of major depressive disorder and are not better explained by another mental disorder (e.g., autism spectrum disorder, posttraumatic stress disorder, separation anxiety disorder, persistent depressive disorder).

    Note: This diagnosis cannot coexist with oppositional defiant disorder, intermittent explosive disorder, or bipolar disorder, though it can coexist with others, including major depressive disorder, attention-deficit/hyperactivity disorder, conduct disorder, and substance use disorders. Individuals whose symptoms meet criteria for both disruptive mood dysregulation disorder and oppositional defiant disorder should only be given the diagnosis of disruptive mood dysregulation disorder. If an individual has ever experienced a manic or hypomanic episode, the diagnosis of disruptive mood dysregulation disorder should not be assigned.

11. The symptoms are not attributable to the physiological effects of a substance or another medical or neurological condition.

Differential Diagnosis: Disruptive Mood Dysregulation Disorder

Bipolar Disorder

• The central feature differentiating disruptive mood dysregulation disorder and bipolar disorders in children involves the longitudinal course of the core symptoms.

  • Bipolar Disorders are episodic, whilst Disruptive Mood Dysregulation Disorder are persistent and long lasting.

Oppositional Defiant Disorder

• The key features that warrant the diagnosis of disruptive mood dysregulation disorder in children whose symptoms also meet criteria for oppositional defiant disorder are the presence of severe and frequently recurrent outbursts and a persistent disruption in mood between outbursts.

  • While most children whose symptoms meet criteria for disruptive mood dysregulation disorder will also have a presentation that meets criteria for oppositional defiant disorder, the Attention-deficit/hyperactivity disorder, major depressive disorder, anxiety disorders, and autism spectrum disorder. reverse is not the case. That is, in only approximately 15% of individuals with oppositional defiant disorder would criteria for disruptive mood dysregulation disorder be met.

  • Mood symptoms of disruptive mood dysregulation disorder are relatively rare in children with oppositional defiant disorder.

Attention-deficit/hyperactivity disorder, major depressive disorder, anxiety disorders, and autism spectrum disorder

• Children whose irritability is present only in the context of a major depressive episode or persistent depressive disorder should receive one of those diagnoses rather than disruptive mood dysregulation disorder.

  • Children with disruptive mood dysregulation disorder may have symptoms that also meet criteria for an anxiety disorder and can receive both diagnoses, but children whose irritability is manifest only in the context of exacerbation of an anxiety disorder should receive the relevant anxiety disorder diagnosis rather than disruptive mood dysregulation disorder.

  • Children with autism spectrum disorders frequently present with temper outbursts when, for example, their routines are disturbed. In that instance, the temper outbursts Intermittent explosive disorder. would be considered secondary to the autism spectrum disorder, and the child should not receive the diagnosis of disruptive mood dysregulation disorder.

Intermittent explosive disorder

• Intermittent explosive disorder does not require the individual’s mood to be persistently irritable or angry between outbursts.

  • A diagnosis of intermittent explosive disorder involving verbal aggression or physical aggression that does not result in damage to property or physical injury to animals or other individuals occurring at least twice weekly can be made after only 3 months of symptoms, in contrast to the 12-month requirement for disruptive mood dysregulation disorder.

  • These two diagnoses should not be made in the same child. For children with outbursts and intercurrent, persistent irritability, only the diagnosis of disruptive mood dysregulation disorder should be made.

Diagnostic Criteria: Major Depressive Disorder

1. Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1)depressed mood or (2) loss of interest or pleasure.

   • Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

   • Markedly diminished interest or pleasure in all or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

   • Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. [Note: In children, consider failure to make expected weight gain.]

   • Insomnia or hypersomnia nearly every day.

   • Psychmotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).

   • Fatigue or loss of energy nearly every day.

   • Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).

   • Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).

   • Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

2. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

3. The episode is not attributable to the physiological effects of a substance or another medical condition.

4. At least one major depressive episode is not better explained by schizoaffective disorder and is not superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or other specified and unspecified schizophrenia spectrum and other psychotic disorders.

5. There has never been a manic episode or a hypomanic episode.

   • Note: This exclusion does not apply if all of the manic-like or

     hypomanic-like episodes are substance-induced or are

     attributable to the physiological effects of another medical

     condition

Differential Diagnosis: Major Depressive Disorder

Manic episodes with irritable mood or with mixed features

• Major depressive episodes with prominent irritable mood may be difficult to distinguish from manic episodes with irritable mood or with mixed features. This distinction requires a careful clinical evaluation of the presence of sufficient manic symptoms to meet threshold criteria. (i.e., three if mood is manic, four if mood is irritable but not manic).

Bipolar I, Bipolar II, or other specified bipolar and related disorder

• Major depressive episodes along with a history of a manic or hypomanic episode preclude the diagnosis of major depressive disorder. Major depressive episodes with a history of hypomanic episodes and without a history of manic episodes indicate a diagnosis of bipolar II disorder, whereas major depressive episodes with a history of manic episodes (with or without hypomanic episodes) indicate a diagnosis of bipolar I disorder.

• On the other hand, presentations of major depressive episodes with a history of hypomania that do not meet criteria for a hypomanic episode may be diagnosed as either other specified bipolar and related disorder or major depressive disorder depending on where the clinician judges the presentation to best fall.

Depressive disorder due to another medical condition

• A diagnosis of depressive disorder due to another medical condition requires the presence of an etiological medical condition. Major depressive disorder is not diagnosed if the major depressive-like episodes are all attributable to the direct pathophysiological consequence of a specific medical condition (e.g., multiple sclerosis, stroke, hypothyroidism).

Substance/medication-induced depressive disorder

• This disorder is distinguished from major depressive disorder by the fact that a substance (e.g., a drug of abuse, a medication, a toxin_ appears to be etiologically related to the mood disturbance. For example, depressed mood that occurs only in the context of withdrawal from cocaine would be diagnosed as cocaine-induced depressive disorder.

Persistent depressive disorder

• This is characterized by depressed mood, more days than not, for at least 2 years. If criteria are met for both major depressive disorder and persistent depressive disorder, both can be diagnosed.

Premenstrual Dysphoric Disorder

• This is characterized by dysphoric mood that is present in the final week before the onset of menses, that starts to improve within a few days after the onset of menses, and that becomes minimal or absent in the week postmenses. By contrast, the episodes major depressive disorder are not temporally connected to the menstrual cycle.

Disruptive mood dysregulation disorder

• This is characterized by severe, recurrent temper outbursts manifested verbally and/or behaviorally, accompanied by persistent or labile mood, most of the day, nearly every day, in between the outbursts. In contrast, in major depressive disorder, irritability is confined to the major depressive episodes.

Major depressive episodes superimposed on schizophrenia, delusional disorder, schizophreniform disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder

• Depressive symptoms may be present during schizophrenia, delusional disorder, schizophreniform disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder. Most commonly, such depressive symptoms can be considered associated features of these disorders and do not merit a separate diagnosis. However, when the depressive symptoms meet full criteria for a major depressive episode, a diagnosis of other specified depressive disorder may be made in addition to the diagnosis of the psychotic disorder.

Schizoaffective disorder

• This differs from major depressive disorder, with psychotic features, by the requirement that in schizoaffective disorder, delusions or hallucinations are present for at least 2 weeks in the absence of a major depressive episode.

Attention-Deficit/Hyperactivity Disorder

• Distractibility and low frustration tolerance can occur in both ADHD and MDD; if the criteria are met for both, ADHS may be diagnosed in addition to the mood disorder. However, the clinician must be cautious not to overdiagnose a major depressive episode in children with ADHD whose disturbance in mood is characterized with irritability rather than by sadness or loss of interest.

Adjustment disorder with depressed mood

• A major depressive episode that occurs in response to a psychosocial stressor is distinguished from adjustment disorder, with depressed mood, by the fact that the full criteria for a major depressive episode are not met in adjustment disorder.

Bereavement

• Bereavement is the experience of losing a loved one to death. It generally triggers a grief response that may be intense and may involve many features that overlap with symptoms characteristic of a major depressive episode, such as sadness, difficulty sleeping, and poor concentration. Features that help differentiate a bereavement-related grief response from a major depressive episode include the following:

  • The predominant affects in grief are feelings of emptiness and loss, whereas in a major depressive episode they are persistent depressed mood and a diminished ability to experience pleasure.

  • The dysphoric mood of grief is likely to decrease in intensity over days to weeks and occurs in waves that tend to be associated with thoughts or reminders of the deceased, whereas the depressed mood in a major depressive episode is more persistent and not tied to specific thoughts or preoccupations.

Sadness

• Periods of sadness are inherent aspects of the human experience. These periods should not be diagnosed as a major depressive episode unless criteria are met for severity (i.e., five out of the nine symptoms), duration (i.e., most of the day, nearly every day for at least 2 weeks), and clinically significant distress or impairment.

Diagnostic Criteria: Persistent Depressive Disorder

This disorder represents a consolidation of DSM-IV-defined chronic major depressive disorder and dysthymic disorder.

1. Depressed mood for most of the day, for more days than not, as indicated by either subjective account or observation by others, for at least 2 years.

   • Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.

2. Presence, while depressed, of two (or more) of the following:

   • Poor appetite or overeating

   • Insomnia or Hypersomnia

   • Low energy or fatigue

   • Poor concentration or difficulty making decisions.

   • Feelings of hopelessness

3. During the 2-year period (1 year for children or adolescents) of the disturbance, the individual has never been without the symptoms in Criteria A and B for more than 2 months at a time.

4. Criteria for a major depressive disorder may be continuously present for 2 years.

5. There has never been a manic episode or hypomanic episode.

6. The disturbance is not better explained by a persistent schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

7. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., hypothyroidism).

8. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Note: If criteria are sufficient for a diagnosis of a major depressive episode at any time during the 2-year period of depressed mood, then a separate diagnosis of major depression should be made in addition to the diagnosis of persistent depressive disorder along with the relevant specifier (e.g., with intermittent major depressive episodes, with current episode).

Specify if:

• With anxious distress

• With atypical features

Specify if:

• In partial remission

• In full remission

Specify if:

• Early onset: If onset is before age 21 years.

• Late onset: If onset is at age 21 years or older.

Specify if (for most recent 2 years of persistent depressive disorder):

• With pure dysthymic syndrome: Full criteria for a major depressive episode have not been met in at least the preceding 2 years.

• With persistent major depressive episode: Full criteria for a major depressive episode have been met throughout the preceding 2-year period.

• With intermittent major depressive episodes, with current episode: Full criteria for a major depressive episode are currently met, but there have been periods of at least 8 weeks in at least the preceding 2 years with symptoms below the threshold for a full major depressive episode.

• With intermittent major depressive episodes, without current episode: Full criteria for a major depressive episode are not currently met, but there has been one or more major depressive episodes in at least the preceding 2 years

Specify current severity:

• Mild

• Moderate

• Severe

Differential Diagnosis: Persistent Depressive Disorder

Major Depressive Disorder

• If there is a depressed mood for more days than not plus two or more persistent depressive disorder Criterion B symptoms for 2 years or more, then the diagnosis of PDD is made. If the symptom criteria are sufficient for a diagnosis of a major depressive episode at any time during this period, then the additional diagnosis of MDD should be made. The comorbid presence of major depressive episodes during this period should also be noted by assigning the appropriate course specifier to the persistent depressive disorder diagnosis as follows:

  • If the individual’s symptoms currently meet full criteria for a Major Depressive Episode, and there have been periods of at least 8 weeks in at least the preceding 2 years with symptoms below the threshold for a full major depressive episode, then the specifier “with intermittent major depressive episodes, with current episode” would be assigned.

  • If full criteria for a MDE are not currently met but there has been one or more major depressive episodes in at least the preceding 2 years, then the specifier “with intermittent major depressive episodes, without current episode” is assigned.

  • If a MDE has persisted for at least a 2-year duration remains present, then the specifier “with persistent major depressive episode” is used.

  • If the individual has not experienced an episode of major depression in the last 2 years, then the specifier “with pure dysthymic syndrome” is used.

Other specified depressive disorder

• Because the criteria for a MDE include symptoms (i.e., markedly diminished interest or pleasure in activities; psychomotor agitation or retardation; recurrent thoughts of death, suicidal ideation, suicide attempt or plan) that are absent from the symptom list for persistent depressive disorder (i.e., depressed mood and two out of six Criterion B symptoms), a very limited number of individuals will have depressive episode have been met as some point during the current episode of illness, a diagnosis of MDD would apply.

• Otherwise, a diagnosis of other specified depressive disorder or unspecified depressive disorder should be given.

Bipolar I and Bipolar II Disorders

• A history of a manic or hypomanic episode precludes the diagnosis of persistent depressive disorder. A history of manic episodes—with or without hypomanic episodes—indicates a diagnosis or Bipolar I disorder.

• A history of hypomanic episodes—without any history of manic episodes in individuals with persistent depressive presentations during which criteria have been met for a major depressive episode—warrants a diagnosis of Bipolar II disorder.

• Other specified bipolar disorder applies to individuals whose presentations include a history of hypomanic episodes along with persistent depressive presentation that has never met full criteria for a major depressive episode.

Cyclothymic Disorder

• A diagnosis of cyclothymic disorder precludes the diagnosis of PDD. Thus, if during the period lasting at least 2 years of depressed mood for most of the day, for more days than not,

  1. There are numerous periods with hypomanic symptoms that do not meet criteria for hypomanic episode.

  2. There have not been any symptom-free periods for more than 2 months at a time.

  3. Criteria have never been met for a major depressive, manic, or hypomanic episode, then the diagnosis would be cyclothymic disorder instead of PDD.

Psychotic Disorders

• Depressive symptoms are a common associated feature of chronic psychotic disorders (e.g., schizoaffective disorder, schizophrenia, delusional disorder). A separate diagnosis of PDD is not made if the symptoms occur only during the course of the psychotic disorder (including residual phases).

Depressive or Bipolar and related disorder due to another medical condition

• PDD must be distinguished from a depressive or bipolar and related disorder due to another medical condition. The diagnosis is depressive or bipolar and related disorder due to another medical condition if the mood disturbance is judged, based on history, physical examination, or laboratory findings, to be attributable to the direct pathophysiological effects of a specific, usually chronic, medical condition (e.g., multiple sclerosis).

• If is judged that the depressive symptoms are not attributable to the physiological effects of another medical condition, then the primary mental disorder (e.g., PDD) is recorded, and the medical condition is noted as a concomitant medical condition (e.g., diabetes mellitus).

Substance/Medication-induced Depressive or Bipolar and related disorder

• This is distinguished from PDD when a substance (e.g., drug of abuse, medication, toxin) is judged to be etiologically related to the mood disturbance.

Personality Disorders

• This is characterized by an enduring pattern of inner experience and behavior that deviates markedly from the expectations of the individual’s culture, with onset by adolescence or early adulthood.

Premenstrual Dysphoric Disorder

1. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week postmenses.

2. One (or more) of the following symptoms must be present:

   • Marked affective lability (e.g., mood swings; feeling suddenly sad or tearful, or increased sensitivity to rejection).

   • Marked irritability or anger or increased interpersonal conflicts.

   • Marked depressed mood, feelings of hopelessness, or self deprecating thoughts.

   • Marked anxiety, tension, and/or feelings of being keyed up or on edge.

3. One (or more) of the following symptoms must be additionally be present, to reach a total of five symptoms when combined with symptoms from Criterion 2 above

   • Decreased interest in usual activities (e.g., work, school, friends, hobbies).

   • Subjective difficulty in concentration.

   • Lethargy, easy fatigability, or marked lack of energy.

   • Marked change in appetite; overeating; or specific food cravings.

   • Hypersomnia or insomnia

   • A sense of being overwhelmed or out of control.

   • Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating” or weight gain.

Note: The symptoms in Criteria 1-3 must have been met for most menstrual cycles that occurred in the preceding year.

4. The symptoms cause clinically significant distress or interference with work, school, usual social activities, or relationship with other (e.g., avoidance of social activities decreased productivity and efficiency at work, school, or home.)

5. The disturbance is not merely an exacerbation of the symptoms of another disorder such as Major Depressive Disorder, Panic Disorder, Persistent Depressive Disorder or a personality disorder (although it may co-occur with any of these disorders).

6. Criterion 1 should confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may made provisionally prior to this confirmation.)

7. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

Differential Diagnosis: Premenstrual Dysphoric Disorder

Premenstrual Syndrome

• It differs from dysphoric disorder in that premenstrual syndrome does not require a minimum of five symptoms nor mood-related symptomatology, and it is generally considered to be less sever than premenstrual dysphoric disorder.

• Premenstrual Syndrome may be more common than Premenstrual Dysphoric Disorder; its estimated prevalence varies with numbers that hover at about 20%,

• While Premenstrual Syndrome shares the same feature of symptom expression during premenstrual phase of the menstrual cycle, the presence of somatic or behavioral symptoms, without the required affective symptoms, likely meets criteria for premenstrual syndrome and not for premenstrual dysphoric disorder.

Dysmenorrhea

• It is a syndrome of painful menses, but this is distinct from a syndrome characterized by affective changes. Moreover, symptoms of dysmenorrhea begin with the onset of menses, whereas symptoms of premenstrual dysphoric disorder, by definition, begin before the onset of menses, even if the linger into the first few days of menses.

Bipolar Disorder, Major Depressive Disorder, and other persistent depressive disorder

• Many women with (either naturally occurring or substance/medication-induced) bipolar or major depressive disorder or persistent depressive disorder believe that they have Premenstrual Dysphoric Disorder. However, when they chart symptoms, they realize that they symptoms do not follow a premenstrual pattern. Because the onset of menses constitutes a memorable event, they may report that symptoms occur only during the premenstruum or that symptoms worsen premenstrually. This is one of the rationales for the requirement that symptoms be confirmed by daily prospective ratings.

• The process of differential diagnosis, particularly if the clinician relies on retrospective symptoms only, is made more difficult because of the overlap between symptoms of premenstrual dysphoric disorder and some other diagnoses. The overlap of symptoms is particularly salient for differentiating premenstrual dysphoric disorder from major depressive episodes, persistent depressive disorder, bipolar disorders, and borderline personality disorder.

Use of hormonal treatments

• Some women who present with moderate to sever premenstrual symptoms may be using hormonal treatments, including hormonal contraceptives. If such symptoms occur after initiation of exogenous hormone use, the symptoms may be attributable to the use of hormones rather than to the underlying condition of premenstrual dysphoric disorder. If the woman stops hormones and the symptoms disappear, then this is consistent with substance/medication-induced depressive disorder.

Other medical conditions

• Women with chronic medical conditions may experience symptoms of premenstrual dysphoria. As with any depressive disorder, medical conditions that could better account for the symptoms should be ruled out, such as thyroid deficiency and anemia.

Diagnostic Criteria: Substance/Medication-Induced Depressive Disorder

1. A prominent and persistent disturbance in mood that predominates in the clinical picture and is characterized by depressed mood or markedly diminished interest or pleasure in all, or almost all, activities.

2. There is evidence from the history, physical examination, or laboratory findings of both (1) and (2):

   • The symptoms in Criterion 1 developed during or soon after substance intoxication or withdrawal or after exposure to or withdrawal from a medication.

   • The involved substance/medication is capable of producing the symptoms in Criterion 1.

3. The disturbance is not better explained by a depressive disorder that is not substance/medication-induced. Such evidence of an independent depressive disorder could include the following:

   • The symptoms preceded the onset of the substance/medication use; the symptoms persist for a substantial period of time (e.g., about 1 month) after the cessation of acute withdrawal or severe intoxication; or there is other evidence suggesting the existence of an independent non-substance/medication-induced depressive disorder (e.g., a history of recurrent non-substance/medication-related episodes).

4. The disturbance does not occur exclusively during the course of a delirium.

5. The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning,

Note: This diagnosis should be made instead of a diagnosis of substance intoxication or substance withdrawal only when the symptoms in Criterion A predominate in the clinical picture and when they are sufficiently severe to warrant clinical attention.

Specify if:

With onset during intoxication: If criteria are met for intoxication with the substance and the symptoms develop during intoxication

With onset during withdrawal: If criteria are met for withdrawal from the substance and the symptoms develop during, or shortly after, withdrawal.

With onset after medication use: If symptoms developed at initiation of medication, with a change in use of medication, or during withdrawal of medication.

Differential Diagnosis: Substance/Medication-Induced Depressive Disorder

Substance intoxication and withdrawal

• Depressive symptoms occur commonly in substance intoxication and substance withdrawal. A diagnosis of substance-induced depressive disorder should be made instead of a diagnosis of substance intoxication or substance withdrawal when the mood symptoms are sufficiently sever to warrant independent clinical attention.

  • For example, dysphoric mood is a characteristic feature of cocaine withdrawal.

• Substance-induced depressive disorder with onset during withdrawal should be diagnosed instead of cocaine withdrawal only if the mood disturbance in Criterion 1 predominates in the clinical picture an is sufficiently severe to be a separate focus of attention and treatment.

Independent Depressive Disorder

• A substance/medication-induced depressive disorder is distinguished from an independent depressive disorder by the fact that even though a substance is taken in high enough amounts to be possibly etiologically related to the symptoms, if the depressive syndrome is observed at times other than when the substance or medications is being used, it should be diagnosed as an independent depressive disorder.

Depressive disorder due to medical condition

• Because individuals with medical conditions often take medications for those conditions, the clinician must consider the possibility that the mood symptoms are caused by the physiological consequences of the medical condition rather than the medication, in which case depressive disorder due to another medical condition is diagnosed. The history often provides the primary basis for such a judgment. At time, a change in the treatment for the medical condition (e.g., medication substitution or discontinuation) may be needed to determine empirically whether the medication is the causative agent.