The Complex Intertwine of MDD and GAD

Initiating and optimizing treatment for patients with Major Depressive Disorder


During the 27th Emirates Mental Health Society International Congress Cognitive, Behavior & Emotional held in Dubai, UAE (29 September to 1 October 2023), a luminary symposium titled "Initiating and optimizing treatment for patients with Major Depressive Disorder" was helmed by Professor Allan Young, Head of School, Academic Psychiatry; Director, Centre for Affective Disorders, at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London. The symposium navigated through the fog of psychiatric co-morbidity. Through a comprehensive exposition, Professor Young delved into the intricate entanglement of major depressive disorder and generalized anxiety disorder. Transitioning into the realm of therapeutic interventions, the symposium spotlighted the efficacy and tolerability of different options in treating major depressive disorder with anxiety symptoms.


Interlinked Shadows and Diagnosis Overlap: The Pervasive Nature of Co-Morbidity Amidst Psychiatric Disorders

The realm of psychiatric diagnoses presents as a fluid spectrum, markedly exhibiting instability over time. A spotlight on a Danish population-based health register cohort study1 unveils a narrative where the veil of one mental disorder scarcely lifts before the face of another is revealed, with all mental disorders significantly elevating the risk for others, a reality undeterred by variations in sex, age, and calendar time.

The domain of psychiatry presents a rich yet challenging tapestry of co-morbidities, embodying a complex landscape where diagnostic realms seamlessly overlap. An exploration into the lifetime prevalence of patients showcasing 1, 2, or 3 psychiatric co-morbidities unveils a staggering propensity toward accumulating additional disorders. “41% of patients with  3 psychiatric disorders met the diagnostic criteria for a fourth disorder; 53% of patients with  2 psychiatric disorders met the diagnostic criteria for a third disorder; and 66% of patients with 1 psychiatric disorder met the diagnostic criteria for a second disorder”.2This prevalence of co-morbidity not only reflects a layered complexity within psychiatric diagnoses but also necessitates a holistic, multidimensional approach in both assessment and therapeutic interventions, endeavoring towards a comprehensive understanding and effective management of the intertwining psychiatric conditions.


GAD & MDD: A Complex Coalescence

Twin studies serve as a window into the intertwined yet distinct domains of Generalized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD), revealing a complex scenario where over 70% of risk factors find common ground in the genesis of these disorders. The shared genetic and environmental underpinnings underscore a narrative where these disorders often dance in tandem, yet with independent rhythms. 3,4,5 When the shadow of anxiety melds with the dusk of depression, the road to remission elongates significantly, painting a challenging picture for affected individuals. A spotlight on remission timelines divulges that half of the patients diagnosed with depression find solace within 6 months, and a similar half diagnosed with anxiety tread towards remission within a span of 16 months. However, the tapestry of co-morbidity unravels a starker reality; less than half of individuals bearing the burden of both disorders manage to stride into the realm of remission over a protracted 24 months.6 This juxtaposition not only highlights the compounding effect of co-morbid GAD and MDD but also accentuates the imperative for a nuanced understanding and tailored therapeutic approaches in navigating the murky waters of psychiatric co-morbidities.

A Beacon of Relief in MDD and Anxiety Co-morbidity

In a compelling pursuit to combat MDD with concurrent anxiety symptoms, a single-arm, open-label prospective study embarked on a 24-week journey exploring one of SSRIs’ efficacy and tolerability among the adult Chinese populace.7 Participants, aged 18-65, with a pronounced episode of MDD and anxiety symptoms (characterized by MADRS score ≥22 and HAM-A score ≥14) were entrusted to the therapeutic alliance of Escitalopram, with dosages ranging between 10-20 mg per day, adjustable post the initial two-week period based on symptom alleviation. The primary outcome spotlighted a high remission rate and a significant descant in MADRS and HAM-A total scores to ≤10 and ≤7 were observed, respectively, at the 24-week milestone. The tale of remission was echoed by 73.7% of the cohort, mirroring an overarching reduction in mean MADRS total score by -26.8 and mean HAM-A total score by -21.6, unveiling a resounding alleviation in the tumultuous tempest of depression and anxiety symptoms. While the journey to remission appeared lengthier for those with higher baseline depression and anxiety scores, the light of relief wasn't dimmed. Encountering an array of treatment-emergent adverse events, with 26.5% reporting at least one such event, the most common culprits being headache and nasopharyngitis, the narrative of safety and tolerability remained largely unscathed. The findings foster hope and open the doors to improved quality of life for individuals wrestling with the dual demons of MDD and anxiety.


  1. Plana-Ripoll O et al. JAMA Psychiatry 2019;76:259-70
  2. Caspi A, Moffitt TE. Am J Psychiatry 2018;175:831-44
  3. Gorwood P. Eur Psychiatry 2004;19:27-33
  4. Kendler KS et al. Arch Gen Psychiatry 1992;49:267-72
  5. Kendler KS et al. Arch Gen Psychiatry 1992;49:257-66   
  6. Penninx BW et al. J Affect Disord 2011;133:76-85
  7. Jiang K et al. Neuropsychiatr Dis Treat 2017;13:515–526