Michelle Di Prisco: Only two bipolar medications work across all three phases – BigGo Finance
After sorting through 116 treatments and 2,510 comparisons of treatment outcomes, the latest evidence map for bipolar disorder came up with a staggering number: Only two drugs show benefit in all three stages of the disease: mania, depression, and long-term maintenance. The score is not just a list of winners, says Michele De Prisco, a psychiatrist and researcher in the Bipolar Disorders and Depression Unit at Hospital Clínic Barcelona. It’s a map of how unbalanced the evidence base is, and how side effects — not just effectiveness — determine whether patients continue treatment. Di Prisco, speaking on Medicine and Science from the BMJ, presented the review along with an interactive tool that allows patients and doctors to adjust drug recommendations based on the side effects patients actually fear.
The same conversation also moved to a different delivery bottleneck. Gillian Turner, a health economist at the Liverpool School of Tropical Medicine, said malaria vaccines were no longer constrained by supply. They are hampered by cold chains, four-dose schedules, local financing, and laborious integration with routine care. This combination makes an explicit point: in both stories, the breakthrough has already occurred. The difficult part is the system that delivers it to the patient.
Bipolar disorder has a phase problem
Di Prisco’s team set out to compile existing reviews, not conduct new drug trials. The result is a comprehensive, living review – a review of reviews – covering 116 distinct treatments and 2,510 associations with treatment outcomes, with a commitment to updating every two years or sooner if key new evidence emerges. The measure aims to solve a real clinical problem: bipolar disorder affects nearly 40 million people worldwide, reduces life expectancy by more than 12 years once comorbid physical and neurological diseases are accounted for, and nearly half of patients do not take their medications as prescribed.
The most clinically relevant structural finding is that the evidence is stratified by stage. Acute mania has many treatment options with strong evidence; Bipolar depression has a much smaller number. Di Prisco’s interpretation is practical, not pharmaceutical.
“Mania is actually not easier to treat than bipolar depression, but it is sometimes more severe… We probably have more treatments available for this stage. Bipolar depression, on the other hand, is actually different, because patients do not have the explosive symptoms that we have in mania. For this reason, it is a more difficult stage to treat, both pharmacologically and practically.”
The review identifies medications that work across outcomes and across stages. The list of cross-stages is short.
| medicine | Mania/hypomania | Depression | maintenance |
|---|---|---|---|
| Quetiapine | ✓ | ✓ | ✓ |
| Olanzapine | ✓ | ✓ | ✓ |
| Lithium | ✓ | Weak evidence | ✓ |
Quetiapine and olanzapine were the only drugs that showed benefit in maintenance, depression, and manic or hypomanic phases. Lithium, the mainstay of treatment, extends to mania and maintenance, but does not include bipolar depression, not necessarily because it doesn’t help, but because the RCT evidence is outdated. The pipeline is moving, too: cariprazine was approved to treat bipolar disorder two years ago, and lumateperone is now being studied, exactly the kind of change the live review was designed to accommodate.
Lithium legacy evidence and side effects trade-off
Lithium is the most counterintuitive case in the review. In the UK, lithium is often the first choice for mood stabilization, however it is not emerging as a multi-stage treatment for bipolar depression. De Prisco is careful not to blame the medication.
“Sometimes studies on lithium are older studies, so they may not have the methodological rigor we expect from newer studies. But in this case, the observational evidence has shown that lithium is a very good treatment for bipolar disorder.”
But even a very good medicine becomes useless if the patient stops taking it. De Prisco links efficacy and tolerability through safety findings reported in the review, which include akathisia, mobility-related side effects, and elevated prolactin.
“A medication can be effective, but if that particular medication is causing them a lot of side effects — a lot of side effects that are important to them — they can also get off that specific medication, which is an important issue.”
This is where the interactive platform, built in the U-Rich framework, goes beyond static review. A patient can raise or lower their concerns about nausea, diarrhea or movement disorders, and the platform reclassifies medications based on the evidence and preferences mentioned.
“It doesn’t make sense to suggest a drug that’s ineffective for a specific patient for a specific condition — but the tool tries to weigh people’s interest in a specific side effect into the recommendation.”
It’s a recommendation logic familiar to anyone who uses consumer apps, but the cost of misclassification is a setback.
What the evidence base still cannot see
DiPrisco is frank about blind spots. Psychosocial treatments exist but are sparse, and often associated with narrow outcomes. Even more surprising is the almost complete absence of cognition, even though cognitive impairment constitutes a major research frontier in bipolar disorder. The reason is structural: a comprehensive review can only combine what clinical trials have measured. If knowledge is not gathered in experiments, it will never reach review.
“If there is no interest or reason to actually look at specific outcomes in RCTs, we will never get information from RCTs.”
The same restriction applies to rare real-world events such as suicide. Randomized controlled trials are simply the wrong tool to capture these outcomes. The platform thus inherits the blind spots of its source material. Di Prisco expects future updates to include more systematic reviews and meta-analyses focused on cognition, although he rates this prediction as low confidence.
Malaria: Display problem solved, delivery problem not solved
Turner’s section begins with the scale: 280 million cases and 600,000 deaths in 2024, concentrated among children under five in sub-Saharan Africa. In the most affected areas, malaria is a disease that mainly affects children.
The good news is tangible: global vaccine supplies are no longer the limiting constraint. The RTS, S, and R21 have all cleared regulatory hurdles, and the supply shortages that previously threatened rollout have been addressed. But Turner immediately reframes the problem.
“Prevention is always better than cure… but vaccines by themselves will not be enough. I think it is really important that the entire range of services is provided.”
Current vaccines reduce severe illness and death in immunized children, but they do not stop parasite transmission or completely prevent infection. This means that they are complementary to bed nets, insecticides and chemical prevention, not substitutes. Layering is the strategy — and Turner points to one study that showed a combined package prevented one in eight infant deaths.
Accepts cold chains, four-dose schedules, and service militia
Turner admits that her research seems less glamorous than the new vaccine.
“You say boring things – that’s what my research is about… People are very excited about new developments, and rightfully so. But really, it’s about the nitty-gritty of tackling those more difficult challenges.”
These difficult challenges are divided into specific delivery problems. The vaccine must remain cold from manufacturer to clinic, which is difficult enough in normal settings and even more difficult in conflict zones. It requires four doses at specific time intervals, which in itself will double parental visits and the workload of health workers. The main solution is to harmonize the schedule: studies have shown that it is possible to give malaria vaccine alongside routine immunization of children, and in countries with seasonal malaria, additional doses can be combined with seasonal malaria chemoprophylaxis.
“The more you can adapt the way you administer these new tools, which in this case are malaria vaccines, to existing conditions, the more efficiently you can deploy them, which also saves money for health systems… but also, the less burden you put on parents.”
Turner cites a truly surprising finding from conflict-affected areas. In parts of the Sahel, by co-providing vaccines with other health services, local militias can see the value of reducing militia resistance to vaccination. The malaria vaccine was actually brought in on the back of services that these armed groups had already accepted.
“By co-providing vaccines with other health services that those militias can see the value of, it has facilitated the introduction of vaccines. So it has overcome some of the hesitation that some of those militias may have had.”
Financing after the aid era
Turner’s sharpest point is about money. This trend occurs with the decline in foreign development aid. She believes that this decline is structural, not a temporary decline, and malaria control programs should be built for a world with less foreign aid. Its reactions move from cheap coordination to more difficult local options.
| Funding response | mechanism | Danger or warning |
|---|---|---|
| Schedule alignment | Co-delivery with routine immunization and seasonal chemoprophylaxis reduces the cost per dose | Requires flexible national protocols |
| Global financing coordination | Gavi, UNICEF, WHO and the Global Fund are leading the procurement and rollout | External financing is declining |
| Local financing | Countries are increasing domestic health budgets | Health spending may cannibalize education budgets |
| Private sector councils | 11 countries invited representatives from governments, non-governmental organizations and the private sector | Justice must remain the handrail |
“What we don’t want to see is an increase in spending on health at the expense of education, because we will see more challenges in the future.”
Turner is pragmatic about private sector engagement. The entry of additional producers into the vaccine market will lead to lower prices; I rated these forecasts with moderate confidence. But she is frank that competition must remain tied to equality.
“Malaria is the catalyst – but it allows for conversations about innovative health financing.”
“As long as there is a need to continue to focus on stocks – this does not necessarily mean engaging the private sector to enhance its profits.”
One concrete institution is the Malaria Control Board: 11 countries have now convened representatives of governments, NGOs and the private sector to talk about local and creative financing. Turner sees this as a motivating model, as malaria creates political interest for talks that benefit the health budget more broadly.
The two stories converge on the same overlooked truth: discovery is no longer the bottleneck; It is delivery. Bipolar review did not require a new drug, but rather a living, interactive evidence system that could translate 2510 comparisons into a decision that the patient and physician could actually use. A malaria vaccine did not require new biology, but rather cold chains, consistent dosing schedules, and a financing model that could withstand declining foreign aid. For anyone looking at biotechnology or global health as an investment topic, the takeaway is practical. The predictable news will continue to make headlines, but the lasting value—and lasting risk—is in the boring part: adherence tools, supply chain logistics, routine immunization integration, and domestic financing. Watch the first two-year update to the U-Rich platform, and see if the 11-country Malaria Council model expands. These are the signals that will separate systems that are expanding from breakouts that are faltering.
