Major Depressive Disorder: The Diagnosis in Numbers, the Treatment Timeline and the Insomnia Problem

Depression is diagnosed on a list, and knowing the list is useful, because the gap between feeling low and meeting the criteria is where a great many people sit undecided for months.

Notice how much of that list is physical. Four of the nine items are body symptoms, which is why a large share of people with depression present to a doctor complaining of exhaustion, poor sleep, weight loss or unexplained aches, and never mention mood at all.

📊 The number that tracks it: PHQ-9

Nine questions, each scored 0 to 3 for how often it has been a problem over the past two weeks, total out of 27. It is used everywhere and it is worth scoring yourself, because the figure is far more useful than trying to recall last month.

Question nine is scored separately in practice. Any answer above zero to the item about thoughts of death or self-harm prompts a direct conversation regardless of the total, and a low total with a positive item nine is not a reassuring result.

Repeating the score every two to four weeks during treatment is the single best way to tell whether something is working, because depression distorts memory of how bad things were.

🩺 What gets ruled out first

Several conditions produce the same picture, and two of them change the treatment completely rather than slightly.

🚨 Safety, said plainly

Thoughts of death or of not wanting to be here are a symptom of the illness rather than a character failure, and they are extremely common in depression. They are also treatable, and they pass as the depression lifts.

• 📞 Thoughts of harming yourself, or of not wanting to go on, mean contacting a doctor or emergency service the same day. Not next week, not at the routine appointment
• 🗣️ Tell one person. The single thing that most changes outcomes is not being alone with it. Being asked about suicidal thoughts does not plant them, and being able to say it out loud reduces their pressure
• 🔒 Reduce access to means. Ask someone to hold medication, firearms or anything else kept for that purpose. This sounds extreme and it is one of the best-evidenced suicide prevention measures there is, because the acute crisis is usually short
• 📝 Write a safety plan while things are calmer — your warning signs, three things that help, three people to contact, and the emergency number — and keep it where you will find it
• ⚠️ The first few weeks of treatment carry a particular risk, especially under 25. Energy and agitation can improve before hopelessness does. Any increase in agitation, restlessness or suicidal thinking after starting or changing a dose needs reporting immediately
• 🍷 Alcohol and depression together raise the risk sharply, because it removes the brake at exactly the wrong moment

⏳ The timeline that decides whether treatment works

More people stop antidepressants because of unmet expectations than because of side effects. The shape of the response is predictable, and knowing it in advance is close to being part of the treatment.

Two practical consequences. A dose should not be abandoned before four weeks unless side effects are intolerable. And side effects usually arrive before benefit, which makes the first fortnight feel like evidence of failure when it is nothing of the kind.

💊 Choosing by what the depression looks like

All the standard antidepressants have broadly similar average effectiveness. What differs is the side effect profile, and that is what the choice is actually made on — matched against the symptoms that are causing the most trouble.

The range is in the antidepressants category, and the broader overview of major depression is in our guide to understanding major depressive disorder.

🌙 Mirtazapine, and the dosing quirk nobody expects

Remeron (Mirtazapine) works differently from the SSRIs, and its side effects are the point rather than the price. For someone who is not sleeping and has stopped eating, a drug that restores both in the first week buys the time the mood effect needs.

• 🔹 Start 15 mg at bedtime. Increase at one to two week intervals to a usual 30 mg, and up to 45 mg daily
• 😴 Sleep improves in the first few nights, long before any mood change. Appetite returns early too
• 🙃 The counterintuitive part: 15 mg is often more sedating than 30 mg. At low dose the antihistamine effect dominates; at higher doses other effects offset it. Someone flattened by grogginess on 15 mg may feel better on 30 mg rather than worse, which is the opposite of the usual instinct to cut down
• 🍽️ Expect increased appetite and weight gain. Helpful when weight has been lost, a genuine drawback otherwise, and worth deciding about in advance rather than discovering
• ✅ Low rates of sexual side effects, which is one of its main advantages over the SSRIs
• 🚫 Not with an MAOI, and sedation is compounded considerably by alcohol
• 🦵 It can worsen restless legs in some people

🔄 If it has not worked

Roughly a third to a half of people do not respond adequately to the first antidepressant, which is normal rather than ominous. The sequence is defined.

1. 🔍 Check it was a fair trial — adequate dose, taken consistently, for at least four to six weeks. A great many apparent failures are under-dosed or intermittently taken
2. 🔎 Re-examine the diagnosis — unrecognised bipolar disorder, ongoing alcohol use, untreated sleep apnea, an underactive thyroid, or persistent ADHD-type difficulty
3. ⬆️ Increase the dose where there has been partial response and tolerance is good
4. 🔁 Switch — within the same class or to a different one. Failing one SSRI does not predict failing another
5. ➕ Augment — adding a second agent, which is specialist territory. Lithium is one of the better-evidenced additions and is also the only treatment with direct evidence for reducing suicide risk
6. 🏥 Specialist referral after two adequate trials have failed, where other treatments exist

And throughout: psychological therapy added to medication outperforms either alone, and the advantage grows after treatment stops, because the skills remain.

📅 How long to stay on it

This is where relapse is created, by stopping as soon as things feel normal — which is the point at which the treatment has just started working rather than finished.

• 📌 At least six to twelve months after feeling fully well, at the same dose that produced the improvement. Not a reduced maintenance dose
• 📌 Two years or longer after two or more episodes, after a severe episode, or where there are ongoing risk factors
• 📉 Stopping is done by tapering over weeks to months, never abruptly. Discontinuation symptoms — dizziness, electric-shock sensations, nausea, irritability, vivid dreams — are commonly mistaken for relapse, and they are worst with paroxetine and venlafaxine
• 📝 Write down what the start of an episode looked like for you while you are well. Early relapse is far easier to treat than a full one, and the early signs are specific to each person and forgotten quickly

🏃 The non-drug part, with the evidence attached

These get called lifestyle advice and two of them have effects that stand comparison with medication in mild to moderate depression.

• 🏋️ Aerobic exercise — around 30 minutes of moderate activity three to five times a week. The effect is substantial and dose-related. The catch is that depression removes the motivation to do the thing that helps, so this works when it is scheduled with someone else rather than left to willpower
• 📅 Behavioural activation — deliberately scheduling activities that used to matter, before wanting to do them. Depression inverts the usual order: in depression, action comes before motivation, not after. Simple, well-evidenced, and the opposite of waiting to feel ready
• 🛏️ Treat the insomnia as its own problem. Cognitive behavioural therapy for insomnia improves depression as well as sleep, and sleep deprivation maintains low mood directly
• 🍷 Reduce alcohol — it reliably worsens mood at a delay of hours, disrupts sleep architecture, and interacts with the treatment
• ☀️ Light therapy in the morning, where there is a clear seasonal pattern
• 👥 Contact with people, including when it is the last thing you want. Withdrawal is both a symptom and an accelerator

📞 When to seek help

Same day:

• Thoughts of suicide or self-harm, a plan, or feeling unable to keep yourself safe
• New or increased agitation, restlessness or suicidal thinking after starting or changing an antidepressant, particularly under 25
• Not eating or drinking, or unable to care for yourself or dependants
• Hearing voices, or beliefs that others would find impossible
• Fever, sore throat or mouth ulcers in the first weeks of mirtazapine — urgent blood count
• Feeling unusually high, wired, or not needing sleep after starting an antidepressant — possible switch into mania

Promptly:

• A PHQ-9 score of 10 or more, or two weeks or more of low mood with loss of interest
• Exhaustion, poor sleep or weight loss with no explanation — ask for thyroid function, full blood count, B12, iron and vitamin D
• Any history of a high or irritable period, or bipolar disorder in the family, before starting treatment
• No improvement at all after four to six weeks at a proper dose — the plan needs changing, not extending
• Drinking to cope, which caps whatever else is tried
• Wanting to stop medication — so it can be tapered rather than stopped
• Memory and confusion in an older person with low mood — this may be treatable depression rather than dementia

❓ Frequently asked questions

📑 Sources and editorial

• Diagnostic criteria for major depressive disorder, including the nine-symptom list and the two-week duration requirement
• Validation studies of the PHQ-9 and its severity bands, and guidance on the handling of item nine
• National and international guidance on the treatment of depression in adults, including severity-matched stepped care, continuation treatment duration and relapse prevention
• Network meta-analyses of antidepressant efficacy and acceptability, and reviews of onset of action and time to response
• Prescribing information for mirtazapine, including dosing, sedation at low versus higher doses, weight gain, and the warning on blood dyscrasias
• Prescribing information for sertraline, escitalopram, bupropion, duloxetine, trazodone and lithium, and reviews of antidepressant discontinuation symptoms
• Evidence on antidepressant-associated switch to mania in unrecognised bipolar disorder, and on bipolar screening before treatment
• Reviews of means restriction and safety planning in suicide prevention, and of lithium and suicide risk reduction
• Meta-analyses of exercise and of behavioural activation in depression, and of cognitive behavioural therapy for insomnia on depressive outcomes
• Reviews of thyroid disease, vitamin deficiency, obstructive sleep apnea and depressive pseudodementia presenting as depression
• Related reading: understanding major depressive disorder, generalized anxiety disorder, depressive pseudodementia, obstructive sleep apnea
• Related products: Remeron (Mirtazapine), Sertafine (Sertraline), Wellbutrin (Bupropion), Desyrel (Trazodone), Cymbalta (Duloxetine), antidepressants category
• RXshop Editorial Team — reviewed by Thomas Walsh, MD — Psychiatrist & Mental Health Specialist