Pharmacotherapy in Bipolar Disorder

The BALANCE Trial: Why Lithium Still Leads in Bipolar I Treatment

Description: The BALANCE Trial (Bipolar Affective disorder: Lithium/ANtiConvulsant Evaluation), published in The Lancet, is one of the largest head-to-head studies comparing long-term maintenance treatments for bipolar I disorder. It directly compared lithium, valproate, and their combination to answer a practical question: Which treatment best prevents relapse? The results made one thing clear — lithium still holds its ground.

The Takeaway

When it comes to preventing relapse in bipolar I disorder, lithium works — and often works best.
What the study found:

• Valproate alone: 69% relapsed or had a major mood episode
• Lithium alone: 59% relapsed
• Lithium + valproate: 54% relapsed

Compared to valproate:

• Lithium reduced relapse risk significantly (HR 0.71)
• Combination therapy did even better (HR 0.59)

Bottom line: Lithium monotherapy outperformed valproate and came close to combination therapy — showing it's still a frontline option.

Why Should You Care

Because relapse in bipolar I disorder can be devastating, and choosing the right maintenance plan can prevent major mood episodes.
One number to know: Patients on lithium alone were 10% less likely to relapse than those on valproate.

The Article

Published in The Lancet, one of the most respected medical journals globally, the BALANCE Trial used a randomized, controlled, multi-center design. That means its findings are both clinically reliable and directly relevant to everyday treatment decisions.

The Clinical Data

Serious adverse events:

• Valproate: 7 events (3 deaths)
• Lithium: 5 events (2 deaths)
• Combination: 4 events (1 death)
  While risks were low across all groups, lithium remained effective and relatively safe.

Study Design: How They Figured It Out

• Study: BALANCE Trial (Bipolar Affective disorder: Lithium/ANtiConvulsant Evaluation)
• Type: Randomized, controlled, international study
• Participants: 330+ adults with bipolar I disorder
• Duration: 24-month follow-up
• Treatments compared:
  • Lithium monotherapy
  • Valproate monotherapy
  • Combination therapy (lithium + valproate)
• Focus: Preventing relapse and tracking serious side effects
  This was one of the most realistic, long-term trials for bipolar I maintenance care.

Why This Study Changed My Practice

In my early years as a psychiatrist, I often leaned toward combination treatments or newer medications. But the BALANCE Trial taught me to pause.
Now I say to patients:
“Sometimes, the most powerful treatment is the one that’s already proven to work.”

What I changed:

• I no longer underestimate lithium — I now consider it first-line for bipolar I
• I’m more cautious with polypharmacy — more meds often mean more side effects
• I help patients see that simplicity isn’t weakness — it’s clinical wisdom
• I reserve combination therapy for more severe or treatment-resistant cases

What Patients Should Know

• Lithium is still the gold standard for bipolar I maintenance
• If you tolerate lithium well, it may give you the best long-term stability
• Valproate alone may not protect against relapse as strongly
• Combination therapy can help in some cases, but adds complexity
• Always weigh side effects, labs, and lifestyle when choosing a plan
• The best treatment isn’t always the newest — it’s the one that works

Final Thought

The BALANCE Trial reminded us that in bipolar I disorder, stability isn’t about complexity — it’s about choosing wisely. Lithium, though decades old, remains one of the most effective tools we have. It’s not just about controlling symptoms — it’s about protecting long-term wellness.

For many, a well-tolerated lithium regimen offers the right balance of simplicity, power, and durability. In bipolar care, doing more isn’t always better — sometimes, it’s about doing what works and sticking with it.

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🔗 Link to the study: https://pubmed.ncbi.nlm.nih.gov/20092882/

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