What is the diagnosis of a bipolar II patient who develops florid psychosis and grandiosity after 2 weeks of imipramine (tricyclic antidepressant) monotherapy?

Substance-Induced Bipolar Disorder (Antidepressant-Induced Mania)

This patient's diagnosis is substance-induced bipolar disorder due to imipramine, specifically an antidepressant-induced manic episode with psychotic features. 1

Diagnostic Classification

The American Academy of Child and Adolescent Psychiatry explicitly states that a manic episode precipitated by an antidepressant is characterized as substance-induced per DSM-IV-TR, even when it represents unmasking of underlying bipolar disorder or disinhibition secondary to the agent. 1, 2 This classification applies regardless of whether the antidepressant "unmasked" a pre-existing condition. 3

Key Diagnostic Features Present

• Florid psychosis with grandiose delusions (believing he is a deity) occurring during a manic episode triggered by imipramine 1, 4
• Temporal relationship: symptoms emerged 2 weeks after starting imipramine monotherapy, which is a tricyclic antidepressant 5
• Baseline diagnosis: Bipolar II disorder, which places him at high risk for antidepressant-induced mood destabilization 1

Critical Diagnostic Distinction: Why This Remains Bipolar II

The diagnosis does NOT automatically convert to Bipolar I disorder simply because psychotic mania occurred. 2 The American Academy of Child and Adolescent Psychiatry clarifies that antidepressant-induced manic episodes maintain their "substance-induced" classification, and this does not change the underlying bipolar subtype from II to I. 2

However, there is an important caveat: if this patient subsequently develops spontaneous (non-substance-induced) manic episodes with psychotic features lasting ≥7 days or requiring hospitalization, the diagnosis would then be upgraded to Bipolar I disorder. 3

Why Imipramine Caused This

The FDA label for imipramine explicitly warns that "hypomanic or manic episodes may occur, particularly in patients with cyclic disorders" and states such reactions may necessitate discontinuation. 5 Tricyclic antidepressants like imipramine have a definite propensity to induce mania in patients with pre-existing bipolar affective disorder. 6

Mechanism and Risk Factors

• Tricyclic antidepressants carry higher switch rates compared to SSRIs in bipolar patients 3, 7
• The patient received imipramine monotherapy without mood stabilizer protection, which violates treatment guidelines 1
• Guidelines explicitly state antidepressants should only be used as adjuncts when the patient is also taking at least one mood stabilizer 1

Immediate Management Algorithm

Step 1: Discontinue Imipramine Immediately

Stop the offending agent as the FDA label indicates such reactions may necessitate discontinuation. 5

Step 2: Initiate Combination Antimanic Therapy

Start lithium or valproate PLUS an atypical antipsychotic simultaneously, as this is the standard approach for acute mania with psychotic features. 1, 2

Specific evidence-based options include:

• Risperidone combined with either lithium or valproate has demonstrated effectiveness in controlled trials for bipolar disorder with psychotic features 2
• Alternative atypical antipsychotics include olanzapine, quetiapine, aripiprazole, or ziprasidone 1

Step 3: Target Therapeutic Levels

• Lithium levels: 0.8-1.2 mEq/L for acute treatment 2
• Obtain baseline labs: CBC, thyroid function, urinalysis, BUN, creatinine, serum calcium, pregnancy test if applicable 2

Step 4: Duration of Antipsychotic Treatment

Continue antipsychotic for at least 4 weeks in combination with mood stabilizer for acute psychotic mania, based on evidence showing lower relapse rates with this approach. 1

Critical Pitfalls to Avoid

Never Use Antidepressant Monotherapy in Bipolar II

This case exemplifies the danger of prescribing antidepressants without mood stabilizer coverage in bipolar patients. 1 The guidelines are unequivocal: antidepressants may destabilize mood or incite manic episodes and should only be adjuncts to mood stabilizers. 1

Recognize High-Risk Features

Patients with Bipolar II who have psychotic depression, family history of bipolar disorder, and rapid-onset depressive episodes with psychomotor retardation are at particularly high risk for antidepressant-induced mania. 1 This patient's presentation with florid psychosis suggests he may have had psychotic features during prior depressive episodes, which occurs in 19.5% of Bipolar II patients. 8

Monitor for Diagnostic Evolution

While the current episode is substance-induced, close monitoring is essential because antidepressant-induced mania may represent unmasking of more severe bipolar illness. 2, 3 If spontaneous manic episodes occur after imipramine discontinuation, the diagnosis would convert to Bipolar I. 3

Long-Term Implications

This patient should never receive tricyclic antidepressants again. 3 If future antidepressant treatment is absolutely necessary for severe depression, consider:

• SSRIs or bupropion (lower switch rates than tricyclics) 3
• Always combined with therapeutic-level mood stabilizer 1
• Close monitoring with structured rating scales like the Young Mania Rating Scale at each visit 2

The presence of psychotic features during this manic episode, combined with antidepressant-induced mania history, indicates higher risk for future mood destabilization and requires aggressive mood stabilization. 2