Bipolar Disorders

Substance/Medication- Induced Bipolar Disorder (BPD)

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Article topic: Substance/Medication- Induced Bipolar Disorder (BPD)

Author: Nadine Absy

Scientific editor: Dr. Ahda Jbara

Linguistic editor: Aroob Awwad.



Substance/medication- induced mental disorders encompass depressive, anxiety-related, psychotic and manic symptoms that result from the usage or abuse of certain medications and/or substances. These symptoms may occur during active use, intoxication or even withdrawal (1).


Etiology and Pathophysiology

Depressive episodes are precipitated by heavy alcohol abuse in almost half of the cases of substance-induced mood disorders (2). Substances that follow alcohol in frequency are cocaine and opioids, particularly heroin. Iatrogenic substances such as anticonvulsants, digoxin, interferon (INF) and corticosteroids may also induce mood disorders. Both drug and substance abuse may induce states of mania or depression (3).

Current standing theories suggest that the substances induce affective states by altering normal neurotransmitter transmission within vital neural circuits. Drug-induced mood symptoms involve changes in dopaminergic, corticotrophin-releasing factor (CRF), neuropeptide Y and serotonergic neurotransmitters (4).



Each etiological substance has its own risk of inducing its respective bipolar disorder. Amongst those diagnosed with bipolar I about 61% have a lifetime prevalence of having a substance-abuse disorder. Therefore, it is crucial to differentiate primary bipolar disorder from substance/medication induced bipolar (5).


Presentation (6)

Patients with substance-induced mood disorders typically present very similarly- if not identical- to patients with independent mood disorders. However, in case of the earlier, the patient’s mood symptoms directly related to the use of substances/medication. In addition, the symptoms resolve following the resolution of severe intoxication or withdrawal.

Usually, severe substance intoxication causes symptoms of either mania or hypomania, while withdrawal is more consistent with symptoms of depression. When the withdrawal phase supplants the intoxication phase, symptoms of agitation, irritability and dysphoria usually predominate.

Depressants commonly induce a state of euphoria, mood liability or poor impulse control. On the other hand, stimulants mimic a manic/ hypomanic episode of BPD and manifest as symptoms of euphoria, loss of appetite, a grandiose attitude, increased energy and paranoia whereas stimulants withdrawal causes the opposite of the aforementioned symptoms, as the patient mostly complains of: depressed mood, apathy, lethargy, and even suicidal ideation.


Differential Diagnoses (7)

Observation of patients during the period in which they have abstained from inciting agents may be a useful way to differentiate substance-induced disorders from primary psychiatric illnesses. A family history of primary psychiatric illnesses can also help in distinguishing the two. A distinction might become more complex when patients have manic symptoms since there is an increased probability of temporal association or causality of mood symptoms following substance use.

The DSM-V cites an important difference between substance/medication-induced bipolar disorder and independent bipolar disorder, which is that patients with independent BPD, unlike those of substance/medication induced BPD, may develop hypomania or mania following the use of antidepressant medications or other treatment. Likewise, patients who develop electroconvulsive-therapy-induced manic or hypomanic episodes that persist beyond the physiological effects of the treatment are diagnosed with independent bipolar disorder not substance/ medication induced bipolar.



For a valid diagnosis the patient must admit to using a substance or a positive laboratory test must be found. The timeline of events provides an easy feature that helps differentiate independent affective disorders from substance-induced ones. Symptoms of substance-induced mood disorders should resolve after stopping the cause of severe intoxication or acute withdrawal symptoms, which can take up to 1 month. A thorough history, laboratory results and imaging studies should be adequate to rule out any other etiology that might be causing the ongoing affective disorder (5).

According to the DSM-V (7) the diagnostic criteria for substance-induced bipolar disorder and related disorders is as follows:

  1. A predominating clear and persistent disturbance in mood distinguished by an expansive, elevated or irritable mood with or without depressed mood, or evidently decreased interest or pleasure in most or all activities.
  2. Physical exam, history or laboratory findings show evidence of: the ability of the inciting substance/medication to produce the symptoms seen in criterion 1, and the development of these symptoms during or following substance intoxication/ withdrawal.
  3. The patient’s symptoms are not better explained by bipolar or bipolar-related disorder independent of substance/medication use. Evidence of an independent disorder may include the following:
  1. Symptoms appear before the onset of substance/medication use.
  2. Symptoms persevere for a considerable period of time (e.g. more than 1 month) after the cessation of acute withdrawal or severe intoxication from the substance/medication.
  3. Other evidence suggesting the presence of an independent BPD (not related to substance/medication use).

D. The disturbances experienced by the patient do not happen exclusively during the course of delirium.

E. The disturbance results in clinically-significant distress or causes significant impairment on the patient’s normal functioning.


Management and Treatment

If a person is diagnosed with a substance-induced mood disorder, this implies that upon the cessation of the inciting substance the disorder should resolve, yet the severity of the episode may at times dictate the need for medication. Whether or not to simply provide supportive care is a decision that depends on the physician’s clinical judgment.

Due to the safety of antidepressants, certain studies support the application and usage of empirical antidepressants in settings where depressive symptoms exist along with evidence of substance abuse (6). For manic symptoms, certain guidelines recommend the usage of second-generation antipsychotics since they have a faster onset of action than mood stabilizers (8)(9).

The most vital aspect of treatment is the emphasis on the importance of abstinence from inciting agents. This should be conveyed to the patient along with treatment modalities in accordance to the inciting substance.



The most compact prognostic factor is adherence to abstinence from inciting agents. Hence, factors that help in sobriety will enable remission. Such factors include psychotherapy, financial stability, compliance to medication, good family ties and social support.

Nonetheless, in the absence of the aforementioned factors, suicide becomes the most serious complication that looms over mood disorders induced by substances. It is worthy to note that studies have found that suicide attempts are more common in substance-induced affective disorders than independent ones. Particularly, a study found that a four-fold increased risk of suicide exists when mood disorders precipitate in setting of substance use (10).



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