1) In diagnosing a Substance/Medication-Induced Mental Disorder, there are three considerations in determining whether there is a causal relationship between the substance use and the psychiatric symptomatology. First, you must determine whether there is a close temporal relationship between the substance or medication use and the psychiatric symptoms. Then, you must consider the likelihood that the particular pattern of substance/medication use could result in the observed psychiatric symptoms. Finally, you should consider whether there are better alternative explanations (i.e., a non-substance/medication-induced cause) for the clinical picture.

 

Consider whether a temporal relationship exists between the substance/medication use and the onset or maintenance of the psychopathology.

    The determination of whether there was a period of time when the psychiatric symptoms were present outside the context of substance/medication use is probably the best (although still fallible) method for evaluating the etiological relationship between substance/medication use and psychiatric symptoms. At the extremes, this is relatively straightforward. If the onset of the psychopathology clearly precedes the onset of the substance/medication use, then it is likely that a non-substance/medication-induced psychiatric condition is primary and the substance/medication use is secondary (e.g., as a form of self-medication) or is unrelated. Conversely, if the onset of the substance/medication use clearly and closely precedes the psychopathology, it lends greater credence to the likelihood of a Substance/Medication-Induced Mental Disorder. Unfortunately, in practice this seemingly simple determination can be quite difficult to discern because the onsets of the substance/medication use and the psychopathology may be more or less simultaneous or impossible to reconstruct retrospectively. In such situations, you will need to rely on the course of the psychiatric symptoms when the person is no longer taking the substance or medication. Psychiatric symptoms that develop during or soon after Substance Intoxication, Substance Withdrawal, and medication use result from the effects of the substance or medication on neurotransmitter systems. Once these effects have been removed (by a period of abstinence after the withdrawal phase), the psychiatric symptoms should spontaneously resolve. Persistence of the psychiatric symptomatology for a significant period of time after the cessation of acute withdrawal or severe intoxication or after stopping a medication suggests that the psychopathology is primary and not due to substance/medication use. The exceptions are the Persistent type of Substance/Medication-Induced Major or Mild Neurocognitive Disorder, in which by definition the neurocognitive impairment continues to be significant after an extended period of abstinence; and Hallucinogen Persisting Perception Disorder, in which following cessation of hallucinogen use, one or more of the perceptual symptoms that the individual experienced with Hallucinogen Intoxication (e.g., geometric hallucinations, flashes of color, trails of images of moving objects, halos around objects) are reexperienced. The DSM-5-TR criteria for substance/medication-induced mental disorder presentations suggest that psychiatric symptoms be attributed to substance use if they remit within 1 month of the cessation of acute intoxication, withdrawal, or medication use. It should be noted, however, that the need to wait 1 full month before making a diagnosis of an independent psychiatric disorder is only a guideline that must be applied with clinical judgment; depending on the setting, it might make sense to use a more extended duration or a shorter duration, depending on your concern for avoiding false positives versus false negatives with respect to detecting a substance/medication-induced mental disorder presentation. On the one hand, some clinicians, particularly those who work in substance use treatment settings, are most concerned about the possibility of misdiagnosing a substance/medication-induced mental disorder presentation as an independent mental disorder that is not caused by substance use and might prefer allowing 6–8 weeks of abstinence before considering the diagnosis to be an independent mental disorder. On the other hand, clinicians who work primarily in psychiatric settings may be more concerned that given the wide use of substances among patients seen in clinical settings, such a long waiting period is impractical and might result in an overdiagnosis of Substance/Medication-Induced Mental Disorders and an underdiagnosis of independent mental disorders. Moreover, it must be recognized that the one-size-fits-all 1-month time frame applies to a wide variety of substances and medications with very different pharmacokinetic properties and a wide variety of possible consequent psychopathologies. Therefore, the time frame must be applied flexibly, considering the extent, duration, and nature of the substance/medication use. Sometimes it is simply not possible to determine whether there was a period of time when the psychiatric symptoms occurred outside of periods of substance/medication use. This may occur in the often-encountered situation in which the patient is too poor a historian to allow a careful determination of past temporal relationships. In addition, substance use and psychiatric symptoms can have their onset around the same time (often in adolescence), and both can be more or less chronic and continuous. In these situations, it may be necessary to assess the patient during a current period of abstinence from substance use or, in the case of a suspected medication-induced psychiatric disorder, to stop the medication suspected of causing the psychiatric symptoms. If the psychiatric symptoms persist in the absence of substance/medication use, then the psychiatric disorder can be considered to be independent. If the symptoms remit during periods of abstinence, then the substance use is probably primary. It is important to realize that this judgment can only be made after waiting for enough time to elapse so as to be confident that the psychiatric symptoms are not a consequence of withdrawal. Ideally, the best setting for making this determination is in a facility where the patient’s access to substances can be controlled and the patient’s psychiatric symptomatology can be serially assessed. Of course, it is often impossible to observe a patient for as long as 4 weeks in a tightly controlled setting. Consequently, these judgments must be based on less controlled observation, and the clinician’s confidence in the accuracy of the diagnosis should be more guarded.

 

In determining the likelihood that the pattern of substance/medication use can account for the symptoms, consider whether the nature, amount, and duration of substance/medication use are consistent with the development of the observed psychiatric symptoms.

    Only certain substances and medications are known to be causally related to particular psychiatric symptoms. Moreover, the amount of substance or medication taken and the duration of use must be above a certain threshold to reasonably be considered the cause of the psychiatric symptomatology. For example, a severe and persisting depressed mood following the isolated use of a small amount of cocaine should probably not be considered to be attributed to the cocaine use, even though depressed mood is sometimes associated with Cocaine Withdrawal. For individuals who are regular substance users, a significant change in the amount used (either a large increase or a decrease in amount sufficient to trigger withdrawal symptoms) may in some cases cause the development of psychiatric symptoms.

 

Consider other factors in the presentation that suggest causes other than a substance or medication.

    These factors include a history of many similar episodes not related to substance/medication use, a strong family history of the particular independent psychiatric disorder, or the presence of physical examination or laboratory findings suggesting that a nonpsychiatric medical condition might be involved. Considering factors other than substance/medication use as a cause for the presentation of psychiatric symptoms requires fine clinical judgment (and often waiting and seeing) to weigh the relative probabilities in these situations. For example, an individual may have a significant family history of Anxiety Disorders and still have a cocaine-induced panic attack that does not necessarily presage the development of an independent Panic Disorder.

 

2) In some cases, the substance use can be the consequence or an associated feature (rather than the cause) of the psychiatric symptomatology. Not uncommonly, the substance-taking behavior can be considered a form of self-medication for the psychiatric condition. For example, an individual with an independent Anxiety Disorder might use alcohol excessively for its sedative and antianxiety effects. One interesting implication of using a substance to self-medicate is that individuals with particular psychiatric disorders often preferentially choose certain classes of substances. For example, patients with negative symptoms of Schizophrenia often prefer stimulants, whereas patients with Anxiety Disorders often prefer CNS depressants. The hallmark of an independent psychiatric disorder with secondary substance use is that the independent psychiatric disorder occurs first and/or exists at times during the person’s lifetime when they are not using any substance. In the most classic situation, the period of comorbid psychiatric symptomatology and substance use is immediately preceded by a period of time in which the person had the psychiatric symptomatology but was abstinent from the substance. For example, an individual currently with 5 months of heavy alcohol use and depressive symptomatology might report that the alcohol use started in the midst of a Major Depressive Episode, perhaps as a way of counteracting insomnia. Clearly the validity of this judgment depends on the accuracy of the patient’s retrospective reporting. Because such information is sometimes suspect, it may be useful to confer with other informants (e.g., family members) or review past records to document the presence of psychiatric symptoms occurring in the absence of substance use.

 

3) In other cases, both the psychiatric disorder and the substance use can be initially unrelated and relatively independent of each other.

    The high prevalence rates of both psychiatric disorders and Substance Use Disorders mean that by chance alone, some patients would be expected to have two apparently independent illnesses (although there may be some common underlying factor predisposing to the development of both the Substance Use Disorder and the psychiatric disorder). Of course, even if initially independent, the two disorders may interact to exacerbate each other and complicate the overall treatment. This independent relationship is essentially a diagnosis made by exclusion. When confronted with a patient having both psychiatric symptomatology and substance use, you should first rule out that one is causing the other. A lack of a causal relationship in either direction is more likely if there are periods when the psychiatric symptoms occur in the absence of substance use and if the substance use occurs at times unrelated to the psychiatric symptomatology.