Bipolar disorder with multiple comorbidities of a 55-year-old female patient: A case report

Abstract

BACKGROUND

Refractory bipolar disorder (BD), characterized by inadequate response to ≥ 2 mood stabilizers with different mechanisms, presents significant therapeutic challenges. The presence of somatic comorbidities such as hypertension and hypothyroidism further complicates treatment due to pharmacodynamic interactions and heightened suicide risk. This report details a successful multidisciplinary management strategy for a 55-year-old female with 32-year refractory BD, hypertension grade 3, and hypothyroidism, providing clinical insights for similar complex cases.

CASE SUMMARY

A retrospective analysis was conducted on a 55-year-old female patient with a 32-year history of BD, comorbid hypertension grade 3 (extremely high risk) and hypothyroidism. The treatment protocol combined mood stabilizers, atypical antipsychotics, modified electroconvulsive therapy, and cognitive behavioral therapy, with simultaneous optimization of somatic disease management.

CONCLUSION

A comprehensive approach combining “mood stabilizer-based polypharmacy, somatic-psychiatric comorbidity management, and integrated physical/psychological rehabilitation” significantly improves prognosis in refractory BD. Long-term follow-up and family support are critical for relapse prevention.

Key Words: Refractory bipolar disorder; Mixed episode; Comorbidity; Individualized treatment; Modified electroconvulsive therapy; Case report

Core Tip: This report details a successful multidisciplinary management strategy for a 55-year-old female with 32-year refractory bipolar disorder, hypertension grade 3, and hypothyroidism, providing clinical insights for similar complex cases.

INTRODUCTION

Refractory bipolar disorder (BD), characterized by inadequate response to ≥ 2 mood stabilizers with different mechanisms, presents significant therapeutic challenges. The presence of somatic comorbidities such as hypertension and hypothyroidism further complicates treatment due to pharmacodynamic interactions and heightened suicide risk[1,2]. This report details a successful multidisciplinary management strategy for a 55-year-old female with 32-year refractory BD, hypertension grade 3, and hypothyroidism, providing clinical insights for similar complex cases.

CASE PRESENTATION

Chief complaints

Alternating episodes of low mood and elevated mood for 32 years, with recurrence of low mood, pessimism, and negativity for 1 week.

History of present illness

Clinical characteristics: Demographics: 55-year-old female farmer from a rural area. Psychiatric history: 32-year illness duration with mixed depressive-mania episodes. 12 hospitalizations; History of inadequate response despite adequate trials: Lithium: 900 mg/day for 8 weeks (serum level 0.8 mmol/L). Valproate: 1000 mg/day for 6 weeks (serum level 65 μg/mL). Quetiapine: 400 mg/day for 4 weeks. Venlafaxine: Discontinued due to anxiety exacerbation. 3 suicide attempts. Comorbidities: Hypertension grade 3 (max BP 180/110 mmHg; currently 150/95 mmHg). Hypothyroidism [thyrotropin (TSH) 3.2 mIU/L; on levothyroxine 50 μg/day]. Current symptoms: Mixed episode: Depressive symptoms [Hamilton Depression Rating Scale-17 items (HAMD-17) = 28] + manic symptoms [Young Mania Rating Scale (YMRS) = 16]. High suicide risk [Columbia-Suicide Severity Rating Scale (C-SSRS) = 8]. Diagnostic assessment: Primary diagnosis: BD, current episode mixed [International Classification of Diseases (ICD)-11: 6A61.3]. Comorbid diagnoses: Hypertension grade 3 (ICD-11: 9C80.3). Hypothyroidism (ICD-11: 5A00). Exclusion criteria: No organic brain lesions [confirmed by computed tomography (CT)], schizophrenia, or substance-induced disorders.

History of past illness

A 15-year history of grade 3 hypertension, with a maximum blood pressure of 180/110 mmHg. Long-term administration of felodipine sustained-release tablets has controlled blood pressure to 140-150/90-100 mmHg. An 8-year history of hypothyroidism, with regular intake of levothyroxine sodium tablets (50 μg/day), and thyroid function is basically stable. No history of other chronic diseases or drug allergies is reported.

Personal and family history

No special personal history or family history.

Physical examination

Decreased appetite, poor sleep (difficulty falling asleep, early awakening), weight loss of 5 kg in the past month; blood pressure 150/95 mmHg, no other significant positive physical signs on examination.

Laboratory examinations

Comorbidities: Hypertension grade 3 (max BP 180/110 mmHg; currently 150/95 mmHg). Hypothyroidism (TSH 3.2 mIU/L; on levothyroxine 50 μg/day). Current symptoms: Mixed episode: Depressive symptoms (HAMD-17 = 28) + manic symptoms (YMRS = 16). High suicide risk (C-SSRS = 8).

Imaging examinations

Cranial CT showed no organic lesions.

FINAL DIAGNOSIS

Primary diagnosis: BD, current episode mixed (ICD-11: 6A61.3). Comorbid diagnoses: Hypertension grade 3 (ICD-11: 9C80.3). Hypothyroidism (ICD-11: 5A00). Exclusion criteria: No organic brain lesions (confirmed by CT), schizophrenia, or substance-induced disorders.

TREATMENT

Pharmacological intervention (Table 1). Non-pharmacological interventions. Modified electroconvulsive therapy (MECT): 6 sessions (twice weekly) during acute phase for rapid suicide risk reduction. Cognitive status monitored using MMSE pre- and post-series. Psychotherapy: Cognitive behavioral therapy (50 minutes × 2/week). Family education (90 minutes × 1/2 weeks). Rehabilitation: Occupational therapy (daily) + social skills training (2 × /week).

Table 1 Treatment protocol.

Drug class	Medication	Dosage regimen	Rationale
Mood stabilizer	Sodium valproate	500 mg → 1500 mg/day	Primary choice for mixed episodes; avoids thyroid interactions
Atypical antipsychotic	Quetiapine	100 mg → 600 mg/day	Guideline-recommended (CANMAT) for mixed features; favorable metabolic profile vs. Olanzapine
Comorbidity management	Felodipine	5 mg/day	BP < 140/90 mmHg

Dosage titration was performed based on clinical response and tolerability. CANMAT: Canadian Network for Mood and Anxiety Treatments.

OUTCOME AND FOLLOW-UP

Symptom improvement

Acute cognitive effects: The patient experienced transient anterograde amnesia immediately following the MECT series, which resolved completely within 4 weeks of discontinuation. No persistent cognitive deficits were observed at the 6-month follow-up (MMSE score stable at 28/30) (Table 2).

Table 2 Clinical outcomes.

Assessment timepoint	HAMD-17 score	YMRS score	Suicide risk (C-SSRS)	Cognitive function (MMSE)
Baseline	22	28	High	24/30
Week 4	12	15	Moderate	26/30
Week 8	6	8	Low	28/30
6-month follow-up	4	6	Very low	28/30

HAMD-17: Hamilton Depression Rating Scale-17 items; YMRS: Young Mania Rating Scale; C-SSRS: Columbia-Suicide Severity Rating Scale; MMSE: Mini-Mental State Examination.

Somatic parameter optimization

Blood pressure stabilized at 135/85 mmHg. Thyroid function maintained within normal range (TSH 0.5-3.5 mIU/L). Valproate serum concentration: 105 μg/mL (week 8) → 92 μg/mL (6-month).

Pharmacokinetic monitoring: A review of potential interactions was conducted using Lexicomp. While valproate (a CYP2D6 inhibitor) and quetiapine (a CYP3A4 substrate) have a known interaction, the patient’s serum levels remained within the therapeutic range without dose adjustment. Felodipine (CYP3A4 substrate) showed no significant interaction with the regimen.

DISCUSSION

Key clinical implications

Treatment resistance mechanisms: Chronic illness duration (32 years), mixed episodes (15%-30% of BD), and comorbidity-driven pharmacokinetic alterations contributed to refractoriness.

Therapeutic innovations: Rationale for valproate + quetiapine: The selection of this specific combination was guided by the 2025 Chinese Guidelines for the Treatment of Bipolar Disorder, which recommend valproate as a first-line agent for mixed episodes[1,2]. Quetiapine was selected over other antipsychotics (e.g., risperidone or olanzapine) due to its dual efficacy in both manic and depressive poles of BD and its lower risk of extrapyramidal symptoms compared to Risperidone, making it suitable for long-term maintenance in this complex case[1,2]. MECT achieved rapid suicide risk reduction (within 2 weeks), consistent with World Federation of Societies of Biological Psychiatry guidelines. Comorbidity management: Avoidance of lithium due to hypothyroidism and use of felodipine (neutral mood effects) optimized safety[1-3].

Limitations and future directions

Single-case design limits generalizability. Long-term cognitive impact of repeated MECT requires longitudinal assessment. Multicenter studies needed to validate this integrated protocol for refractory BD with somatic comorbidities.

CONCLUSION

This case demonstrates that a multidisciplinary strategy combining pharmacotherapy (valproate + quetiapine), MECT, psychotherapy, and comorbidity optimization can effectively manage refractory BD with multiple somatic diseases. Sustained remission over 6 months underscores the importance of individualized treatment, family engagement, and long-term follow-up in chronic BD management.