Continuing Education Activity

Substance-induced disorders include, among other disorders, substance/medication-induced mental disorders. Substance/medication-induced mental disorders refer to depressive, anxiety, psychotic, or manic symptoms that occur as a physiological consequence of the use of substances of abuse or medications. It may occur during active use, intoxication or withdrawal. This activity outlines the epidemiology, presentation, diagnosis, clinical evaluation, psychopathology, and treatment of substance/medication-induced mental disorders covering depression and bipolar by an interprofessional team.

Objectives:

• Describe the epidemiology of substance/medication-induced disorders.
• Outline the typical presentation of alcohol, cocaine, or opioid-induced mood disorders.
• Summarize the treatment options for substance/medication-induced disorders.
• Review the importance of an interprofessional approach in treating patients with substance/medication-induced disorders.

Introduction

Although, both illicit substances and iatrogenic medications are ingested with the impetus to alleviate mood, a substantial proportion of patients experience paradoxical affective disorders following the ingestion of said substances. Instead of the prosaic euphoria experienced while intoxicated or the subsequent day 'hangover,' some individuals will become manic or enter into a state of depression. Mood disorders that precipitate only in association with substance use are specified as 'substance-induced.' Affective disorders that can precipitate in the setting of substance use include both bipolar and related disorders and depressive disorders. These disorders were previously found within the nosological category of substance-induced mood disorders, in DSM-IV. However, in the current DSM 'substance-induced' is now a specifier for mood disorders.

Depression and bipolar disorder frequently co-occur with substance use disorders (SUDs) and are prevalent in the general population.[1][2] This review will reflect on both substance-induced depressive disorder and substance-induced bipolar and related disorders, and further elaborate on how they can be distinguished from mood disorders that are comorbid with SUDs.

For the purpose of this review, the designation of substance-induced mood disorders - although no longer a distinct category in DSM-V - will represent both substance-induced depression and bipolar disorders.

Etiology

Substance-induced disorders may develop in the context of either intoxication or withdrawal. Of the depressive episodes occurring in the general population, nearly half precipitate in the context of heavy alcohol use.[3][4][5] The next most frequently associated substances are cocaine and opioids, especially heroin. Iatrogenic substances can also induce pathological affective states. Examples of such medications include interferon (IFN), corticosteroids, digoxin, and antiepileptic drugs.[6][7] Either class - substance or medication - can induce states of mania or depression. Current theorists posit that the aforementioned substances alter neurotransmitter transmission within important neural circuits, such as the mesolimbic tract and Papez circuit.[8] 

Recent evidence has also revealed that genes increase diathesis for both substance use disorders as well as mood disorders.[9] 

Epidemiology

Current research estimates the lifetime prevalence of substance-induced depressive disorders between 0.26% and 1%.[10][1] Of those with alcohol use disorder, it is estimated that 40-60% experience substance-induced depression.[5][11][12] Data gathered from outpatient participants with opioid use disorder reported that around 55% of these participants had a substance-induced depression.[13] Of the individuals with major depression, 16.5% have an alcohol use disorder, and 18% have a drug use disorder. Additionally, data indicate that the lifetime prevalence of substance use disorders in bipolar I patients is 61%.[14] 

Pathophysiology

The pathophysiology of substance-induced disorders remains a topic of ongoing discussion. Drug-induced mood symptoms precipitate changes in cerebral structures, such as the frontal cortex, nucleus accumbens, olfactory tubercle, hippocampus, amygdala, and hypothalamus.[15] Drug-induced mood symptoms involve alterations of serotonergic, dopaminergic, corticotropin-releasing factor (CRF), and neuropeptide Y (NPY) neurotransmitter activity.[16][17] 

History and Physical

Patients with substance-induced affective disorders will present similarly to patients with independent mood disorders with or without comorbid substance use disorders. Thus, patients may endorse sad mood, insomnia, feelings of guilt, suicidal ideation, psychomotor retardation, distractibility, hopelessness, helplessness, irritability, decreased libido, anergy, or anorexia if depressed. In the setting of mania, the patient will endorse grandiosity, distractibility, impulsivity, pressured speech, racing thoughts, sexual promiscuity, irritability, insomnia, and increased energy.

The anamnesis of a patient experience a substance-induced affective disorder will consist of mood symptomatology in direct temporal relation to the ingestion of the substance. These symptoms will resolve following the cessation of severe intoxication or acute withdrawal (up to 1 month). Generally, severe intoxication produces symptoms consistent with mania or hypomania, whereas withdrawal manifests as symptoms of depression. Depressants (e.g. alcohol, sedative-hypnotics, analgesics, etc) may induce states of euphoria, decreased impulse control, or mood lability. This intoxication phase is then supplanted by a withdrawal phase, most notable for irritability, agitation, and dysphoria. Stimulant use (e.g. cocaine, amphetamines, etc.) can mimic bipolar spectrum disorders by producing euphoria, increased energy, anorexia, grandiosity, and paranoia. Stimulant withdrawal can cause anhedonia, apathy, depressed mood, and suicidal ideation.[9] 

Evaluation

The substance-induced mood disorder will mimic its corresponding independent affective disorder. Thus, substance-induced depression will follow diagnostic criteria used to evaluate for depressive disorders, and substance-induced bipolar disorder will reflect that of the bipolar spectrum disorders. As implied by the title 'substance-induced', either admission of the ingestion of a substance or a positive laboratory test is necessary for a valid diagnosis. Temporality is the easiest feature to differentiate an independent affective disorder from a substance-induced one. As mentioned previously, symptoms of a substance-induced mood disorder will resolve following the cessation of severe intoxication or acute withdrawal (up to 1 month).[14] For substance-induced depressive disorder, the clinical picture is characterized by a depressed mood or a markedly diminished interest or pleasure in all spheres of life, and the symptomatology is corroborated with the history, physical examination, or laboratory findings. For the substance/medication-induced bipolar, the clinical picture is delineated by an elevated, expansive, or irritable mood, with or without depressed mood, or markedly diminished interest or pleasure in all spheres of life. Clinical evidence is corroborated with the history, physical examination, or laboratory findings.

Laboratory results and imaging, as well as a detailed history, should rule out other etiologies of the ongoing affective disorder. 

Treatment / Management

Implicit with the diagnosis of substance-induced mood disorder is the implication that the disorder should resolve spontaneously, following the cessation of the inciting irritant. However, the severity of a substance-induced affective episode may necessitate the application of medication. Clinical judgment, corroborated with a proper history and collateral information, will aid the clinician's decision whether to simply offer supportive care while observing the patient in a safe environment during the withdrawal period or to treat the active affective disorder. Because of the relative safety of most antidepressants, some studies suggest the empiric application of antidepressants in the setting of depressive symptomatology and co-occurring substance use.[14] For manic episodes, guidelines recommend second-generation antipsychotics, such as quetiapine or olanzapine, as they are faster acting than mood stabilizers.[18][19][20] 

The most essential feature of treatment should be the emphasis on abstinence from the inciting substance. The treatment modality will vary depending on the substance of preference of the patient. 

Differential Diagnosis

Transient substance-induced disorders may be differentiated from a primary psychiatric illness through observation during a period of abstinence with a temporal association of the intake of a substance. A family history of a primary psychiatric illness may also facilitate distinction. For substance-induced symptoms of mania, the differentiation may be more complex because of a high probability of temporal association or causality of mood symptoms after substance use.[9][3][4]

Prognosis

In theory, the mood symptoms should extenuate following a period of sobriety. Maintenance of said abstinence is the most robust prognosticative factor for subsequent episodes. Thus, invariably, factors that promote sobriety will potentiate remission. Familial support, psychotherapy, financial stability, and medication compliance are all factors that promote sobriety. Recipricolaly, settings which increase the risk of substance use are associated with poorer prognoses. 

Complications

The most significant complication looming over substance-induced mood disorders is suicide. Studies reveal that suicide attempts are more common in affective disorders that are substance-induced. One study estimated an almost four-fold increased risk of suicide attempts when the mood disorder precipitates in the setting of substance use.[21] 

Deterrence and Patient Education

• Refrain from the use of alcohol or illicit drugs.
• Avoid people or milieu that most likely trigger the use of alcohol or illicit drugs.
• Consider psychosocial interventions like AA and NA to promote recovery from alcohol and substance abuse.
• Discuss with a physician about any new medication prescribed by another physician because some medications can cause mania or depression.
• Contact a physician if having concerns regarding over the counter medicines because some OTCs can augment the effects of other medications and may cause mania or depression.
• Eat a healthy diet, limit caffeine, and quit smoking. 
• Be aware of depression or mania that result after the initiation of substance use or use of medication and discuss them with your primary care physician or psychiatrist.

Enhancing Healthcare Team Outcomes

Managing substance-induced disorders disorder requires a multidisciplinary approach involving the patient, the patient’s family, physician, nurse, and therapist. Although substance-induced disorders (depression and bipolar) subside after the biological effects of the drug fade, vulnerable individuals can develop a full-blown major depressive disorder or bipolar disorder, without proper management, psychiatric and medical complications can be fatal. 

In the emergency department, physicians and assigned nurses are responsible for coordinating the care, which includes the following:

• Drug levels in the blood and or urine
• Monitor the patient for signs and symptoms of respiratory depression and cardiac arrhythmias.
• Administer benzodiazepines or antipsychotics for acute mania.
• Creatine phosphokinase (CPK) to rule out rhabdomyolysis 
• Provide rehydration with normal saline
• Provide 1:1 for safety (suicide and injury to others)
• Consider involuntary status for imminent threats to self and others
• Physical restraints as the last result
• Consult an addiction specialist

In the outpatient clinic physician and assigned nurse are responsible for:

• Assure the patient’s safety and others in case of acute mania or severe depression.
• Transport the patient to the emergency department.
• Consider an involuntary commitment to a psychiatric hospital for imminent threats to self and others.

Physicians, nurses, and therapists should discuss and involve the family in the treatment plan. An interprofessional team that provides a holistic and integrated approach can help achieve the best possible outcomes.