When a medicine stops working

When a medication appears to stop working, the instinct is to increase the dose or change the drug, and the more common explanations sit elsewhere.

The explanations, in order of frequency

Adherence. Around half of people taking long-term medication do not take it as prescribed, and this is by a wide margin the most common reason treatment appears ineffective.

It is rarely deliberate: forgetting, complexity, cost, side effects and not understanding the purpose account for most of it.

Clinicians frequently do not ask, and patients frequently do not volunteer.

Technique, which applies to inhalers, injections, eye drops and topical preparations, where incorrect use means the drug never arrives.

Interactions, where a newly added medicine, an over-the-counter product or a supplement reduces the effect.

Progression of the underlying condition, which is a genuine explanation and is generally assumed too early.

A new condition producing similar symptoms.

Tolerance, which is genuine for some drug classes and rare for most.

And a change in formulation or manufacturer, which matters for a small number of narrow therapeutic index drugs.

Adherence, examined honestly

Because this is where the answer usually is.

The useful question is not whether you take it but how many doses you have missed in the past week, asked in a way that makes an honest answer easy.

Common patterns: stopping when feeling better, which is particularly common with antidepressants and antihypertensives; taking it only when symptomatic, which defeats preventive medications entirely; skipping doses to make a prescription last; and stopping because of a side effect without telling anyone.

Practical fixes: pill organisers, blister packs, synchronising prescriptions, simplifying regimens, once-daily formulations, combination tablets, and linking doses to existing routines.

And telling the prescriber the truth, since a dose increase on top of missed doses is both ineffective and unsafe.

Interactions worth checking

Common culprits.

St John's wort, which induces liver enzymes and reduces the effect of contraceptives, anticoagulants, immunosuppressants and several others.

Antacids, calcium, iron and some other minerals, which impair absorption of several drugs including thyroid replacement and some antibiotics.

Grapefruit juice, which affects the metabolism of a number of medicines.

Enzyme-inducing drugs including some anti-epileptics and rifampicin.

Non-steroidal anti-inflammatories, which reduce the effect of antihypertensives.

Smoking, which induces enzymes affecting some medications — and stopping smoking can therefore raise levels, which requires dose review.

And alcohol.

Where tolerance is real

A short list.

Opioids, where tolerance develops reliably.

Benzodiazepines and Z-drugs, where hypnotic effect diminishes within weeks.

Nitrates, where continuous exposure produces tolerance, which is why nitrate-free intervals are built into dosing.

Some decongestants, where rebound occurs.

And short-acting reliever inhalers, where increasing use reflects worsening control rather than tolerance.

For most other classes — antihypertensives, statins, antidepressants, thyroid replacement — true tolerance is not the usual explanation.

The specific case of antidepressants

Where this question arises frequently.

Apparent loss of effect after a period of successful treatment has several explanations: adherence, a new stressor, an emerging different condition, alcohol or substance use, an untreated physical condition such as thyroid disease or sleep apnoea, and genuine loss of response, which is described.

Options include dose adjustment, switching, augmentation and adding psychological therapy.

Stopping abruptly is not among them, since discontinuation symptoms are real and can be prolonged.

What to bring to the review

Making the appointment productive.

An honest account of adherence.

A complete list of everything you take, including over-the-counter products, supplements and anything bought online.

When the change happened and what else changed around then.

Any measurements — blood pressure readings, peak flow, symptom diaries, blood glucose — which turn a subjective impression into data.

What side effects you are experiencing, since these are frequently the unspoken reason for reduced adherence.

And what matters most to you, since the treatment goal may need revisiting.

Before increasing the dose

The questions worth asking.

Is my technique correct?

Am I actually taking it as prescribed?

Could anything else I take be interfering?

Has the condition changed?

Is there another explanation for these symptoms?

Would a different drug in the same class be better tolerated?

And is this still the right treatment goal, which is a question that becomes more relevant with age and with multiple conditions.

General information only, not medical advice. Consult a clinician or pharmacist if a medicine seems less effective, and do not adjust doses yourself.