Lift Your Mood

In detail

Move most days, hard enough that talking is work: walking fast, jogging, lifting, a class. Lift twice a week. Training with other people, or with a coach, did the most.

Found

Medium effect on depression. An umbrella of 1,079 trials and 79,551 people: exercise cut depression by a moderate effect, aerobic work the most. The biggest gains were at ages 18 to 30, and in group or supervised sessions. Across 218 trials, walking or jogging, yoga and lifting led.

Why

Training raises the growth signals the brain uses to remodel, burns down the day's stress hormones, and gives the next morning's HRV something to rise from. It is the one move on this page that also fixes the sleep.

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Musculoskeletal injury

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In detail

Plan the week in advance: one thing you used to enjoy and one small task you have been avoiding, each day, at a set time. Do it whether or not you feel like it. Note the mood before and after.

Found

Medium effect over the comparison group. 105 trials, 13,933 people: behavioral activation beat control conditions by a moderate to large effect, and the gain held at twelve months. Done alone from a book or an app, it still worked.

Why

Low mood makes you drop the things that used to feed it, and dropping them deepens the low. Scheduling them back in breaks the loop from the action side. The mood follows the doing.

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In detail

Seven to eight hours, the same wake time seven days a week. If you are not sleeping, run Deeper sleep first. This page rides on it.

Found

g = 0.63 on depression. Sixty-five trials, 8,608 people: when a treatment improved sleep, depression fell by a medium effect. Anxiety and brooding fell with it. The more sleep improved, the more mood did.

Why

A short night raises the amygdala's reactivity and cuts the prefrontal brake on it the next day. Regular sleep is the one move here that every other move depends on.

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Nine hours or more a night that does not refresh is a doctor's question, not a reason to sleep in.

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In detail

Count the drinks for a week, then cut a level: from most nights to some, from some to few. The smaller glass, every round. A month off if the count surprises you.

Found

1,383 people, one year. 1,383 people, one year: every step down the risk-drinking ladder came with fewer alcohol consequences and better mental health, at the end of treatment and a year on. A bigger step meant a bigger gain.

Why

Alcohol sedates on the way down and rebounds on the way up. It breaks the second half of the night, drops the next morning's HRV, and leaves the anxiety it promised to take. Cutting the count gives the mood its mornings back.

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Physical dependence, where cutting abruptly is a medical event and not a plan

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In detail

Thirty minutes of a 10,000-lux box, or the sky, inside an hour of waking. Every day, including the gray ones.

Found

23 trials, 1,120 people. Twenty-three trials, 1,120 people: light therapy beat the comparison treatments on depression scores, a mild-to-moderate effect, outside the winter kind of low mood.

Why

Light in the first hour sets the clock in the hypothalamus, and the same pathway runs into the circuits that set mood. A late, weak clock is a flat morning.

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Mania or hypomania switch in bipolar disorder

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In detail

Pick one person and tell them how the last few weeks have really been. Then keep a standing plan with people each week: a training partner, a meal, a call.

Found

Odds 0.76 of depression. Over 100,000 people screened for 106 lifestyle factors, then tested with genetic methods for cause and effect. Confiding in others held up as protective against depression, with odds of 0.76.

Why

Isolation and low mood feed each other. Saying it out loud to one person breaks the silence that keeps a man stuck. People are also where most good moments come from.

In detail

Each night, write three things that went well today and why each one happened. Two minutes, on paper or the phone.

Found

64 trials. Sixty-four trials: gratitude exercises brought more gratitude, better mental health, and fewer symptoms of anxiety and depression. They also lifted mood and positive emotion.

Why

Low mood tilts attention toward what went wrong. Writing down what went right, and why, trains the eye back, and the why links the good moment to something you can repeat.

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In detail

Pick one exercise and keep it up for weeks. Write out your best possible future self, use a strength in a new way each day, or do one kind act.

Found

Small effect on wellbeing. Thirty-nine studies, 6,139 people: positive psychology exercises raised wellbeing and cut depression by small effects that held at three to six months. Longer programs did more.

Why

These train the positive side directly: hope, meaning, and a sense of using what you are good at. They do not wait for the low to lift first.

In detail

A short sitting, eyes closed: wish yourself well, then someone close, then a stranger, then everyone. Short phrases, repeated. Use a recording to start.

Found

23 studies. Twenty-three studies: loving-kindness practice raised compassion and positive feeling and lowered negative feeling and symptoms. It matched other proven therapies, in any format or length.

Why

It trains warmth on purpose, toward yourself first. That runs against the self-criticism low mood feeds on.

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In detail

A yoga class, or 30 minutes at home from a video, twice a week, for eight to twelve weeks. It counts as your movement on those days.

Found

g 0.55 on depression. Across 218 trials of exercise for depression, yoga was one of the forms that moved it most, with walking, jogging and lifting, and it was among the easiest to stick with.

Why

Slow breathing and long holds tip the autonomic balance toward the calming branch, the loading is real training, and the attention is meditation. It is three moves from this page in one hour.

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Rare serious neurovascular & structural events

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In detail

30 mg a day of a standardized stigma extract, as 15 mg twice a day, for six weeks. A named standardized extract or nothing: saffron is the most adulterated spice there is.

Found

4.4 points off BDI, 14 trials. Thirty-four trials, 1,769 people in all. On the Beck scale, 14 trials and 817 people: depression down 4.4 points against placebo. Head to head with SSRIs in eight trials, saffron matched the SSRIs, with fewer side effects.

Why

Crocin and crocetin carry it, and crocetin is small enough to cross into the brain. The trials measure it on the self-rated scales more than on the doctor's, which is where the effect sits.

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Mild stomach upset or headache in some. High doses of the spice itself are unsafe; stay at the trial dose. It may add to antidepressants and to blood thinners: on either, ask the doctor first. With bipolar disorder, ask first: it can lift mood too far.

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In detail

The standardized extract, 900 mg a day in three doses, for six weeks, for mild to moderate low mood. Clear it against every other pill you take first: it switches on the liver enzymes that clear half the pharmacy. Never with an antidepressant.

Found

29 trials, 5,489 people. Twenty-nine trials, 5,489 people: the extract beat placebo on response and matched the standard antidepressants, with fewer dropouts for side effects. Thirty-five trials, 6,993 people: more responders than placebo, and it matched antidepressants in mild and moderate low mood.

Why

Hyperforin blocks the reuptake of several transmitters at once, which is the antidepressant action. The same molecule induces the liver's drug-clearing enzymes, which is why the interaction list is the longest on this page.

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It weakens many medicines: seizure drugs such as phenytoin and carbamazepine, digoxin, simvastatin, some cancer drugs, warfarin, HIV and transplant drugs, and some antidepressants. Serotonin syndrome on top of an SSRI. Sun sensitivity.

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In detail

800 mg twice a day, for six weeks. Never on top of an SSRI without your doctor's say-so: it is a serotonin drug in all but name.

Found

Medium effect over placebo. Twenty-three trials, 2,183 people: SAMe alone beat placebo on depressive symptoms by a moderate effect, with dropouts no higher. Added to an SSRI that had failed: 36% responded against 18% on placebo.

Why

It is the body's methyl donor, feeding the synthesis of the transmitters the antidepressants act on. That is also why it can push serotonin too far in company.

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Serotonin syndrome with drugs that raise serotonin. Mania or hypomania, even without a bipolar diagnosis. Gut upset.

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In detail

Fish oil where at least 60% of the omega-3 is EPA, up to 1 g a day of it, with food. Eight weeks before you judge it.

Found

26 trials, 2,160 people. Twenty-six trials against a placebo, 2,160 people: omega-3 lowered depression symptoms overall. Formulas at least 60% EPA, at up to 1 g a day, carried the effect.

Why

EPA is built into cell membranes and shifts the body toward less inflammatory signals. Inflammation runs high in a share of low mood, which is where the EPA effect sits.

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Atrial fibrillation risk rises with the dose, higher above 1 g a day. On a blood thinner, ask the doctor first.

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In detail

Curcumin extract, 500 mg twice a day with food, for eight weeks before you judge it. The trials mostly added it beside the other moves. Stop at any yellowing of the eyes.

Found

g 0.75 on depression. Ten trials, 531 people: curcumin lowered depression scores by a large effect, and it was generally well tolerated. In an eight-week trial at 500 mg twice a day, it pulled ahead of placebo on mood between weeks 4 and 8.

Why

Curcumin calms the inflammation and cell-stress signals that run high in some low mood. It also acts on the stress-hormone system and on serotonin and dopamine.

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Blood sugar rose on curcumin in one trial: with diabetes or raised blood sugar, ask a doctor first and watch your HbA1c. Stomach upset in some. Rare liver injury has been reported with turmeric and curcumin supplements: stop at yellowing of the eyes or dark urine. It can add to the bleeding risk of blood thinners: on one, or before surgery, ask first. With gallstones, ask first.

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In detail

Start the guided quest, built on the methods tested in trials and done on your own: a lesson every five days or more, and a short log every day. Lesson 1, see how mood follows doing. Lesson 2, plan one thing that matters to you each day, and do it. Lesson 3, break the task you have been avoiding into small steps. Then catch and test the low thoughts, solve one problem at a time, and write your plan for a bad week.

Found

Thirteen trials, 3,876 people, pooled person by person: the self-guided online course lowered depression and nearly doubled the odds of a response, one extra person better for every 8 who did it. The more of it people finished, the better they did. Across 39 trials, courses with a guide and courses done alone both beat control, and at 6 and 12 months they matched.

Why

Low mood runs on a loop: you do less, so less goes right, so you feel worse. The log shows the loop in your own week, and the plan and the small steps break it from the doing side. The skills stay with you when the course ends.

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A PHQ-8 of 15 or more, or a score that climbs two check-ins running, is a reason to see the doctor before you carry on.

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In detail

When the mood drops, write down the thought that came with it, word for word: "I always mess it up." Under it, list the evidence for it and the evidence against it. Then write a fairer line, the one you would say to a friend. On paper or in a self-help website built on the methods tested in trials, a few times a week.

Found

A trial of 525 people: an online self-help course that taught this cut depression scores by 3.2 points against a control, and a plain information site about low mood worked too.

Why

Low mood speaks in absolutes: always, never, nobody. Writing the thought down turns it from a fact into a claim, and a claim can be checked. The fairer line takes the charge out of it.

In detail

An eight-week mindfulness course you follow on your own, online or from a book with recordings: one new lesson a week and a short guided sitting every day. Notice a low thought as a passing event, not a fact. Best started once the worst has lifted.

Found

g 0.29 on depression. Fifteen trials of online mindfulness courses: small but real gains on depression, anxiety and wellbeing, and a moderate one on stress. More sessions went with bigger gains on stress.

Why

It trains you to notice a low thought early, as something passing through, before it spirals. Practiced daily, the noticing becomes the habit.

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Can be hard going when thoughts are intense or very distressing. Start it once the worst has passed, and keep the sittings short.

In detail

Early research. Creatine monohydrate beside an antidepressant or the self-help course, not in place of them. The trials used 2 to 10 g a day for 4 to 8 weeks.

Found

d 1.13 beside an SSRI. Five trials in mental disorders, four in major depression. Beside escitalopram it beat the SSRI alone, d 1.13 at 8 weeks, and beside CBT it beat CBT alone.

Why

Creatine tops up the brain’s fast energy store. In the depression trials, the gains were largest where brain energy markers rose.

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Two of 17 people in the trial had a manic or hypomanic spell. A little water weight.

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In detail

Early research. Get the blood level checked first. If it is low, 2,000 IU a day. Never a megadose.

Found

Large effect, varied. Thirteen studies, seven pooled: taking vitamin D lowered depression scores against comparisons, by a large margin. The result varies from trial to trial.

Why

Vitamin D acts as a hormone, and its receptor sits in brain regions that set mood. Topping up a low level is the aim, not a high one.

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Too much raises blood calcium and can hurt the kidneys. Megadoses and very high daily doses are where the harm is.

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In detail

Early research. Magnesium, 248 mg of elemental magnesium a day, the trial dose, for six weeks before you judge it. Split it through the day if it loosens the gut.

Found

PHQ-9 down 6 points. Seven trials, 325 people: magnesium lowered depression scores against placebo. In a six-week trial of 248 mg a day, PHQ-9 scores fell 6 points more than on no supplement, and it was well tolerated.

Why

Magnesium damps the NMDA glutamate receptor, the same target the fast-acting depression drugs hit.

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Loose stools, the most common. With kidney disease, ask first: it can build up. It cuts the absorption of some antibiotics and thyroid tablets, so take them hours apart.

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In detail

Early research. Zinc, 25 mg a day with food, beside an antidepressant, for twelve weeks. Never above the trial dose: long-term high doses drain copper.

Found

Small effect, added to a drug. Five trials pooled: zinc added to antidepressants lowered depression scores more than placebo. In a twelve-week trial at 25 mg a day, it sped up and strengthened the response, most of all where the pills had not helped before.

Why

Zinc blocks the NMDA glutamate receptor, the target of the fast-acting depression drugs, and seems to help an antidepressant do its job.

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Nausea on an empty stomach. Long-term high doses cause copper deficiency, with anemia and nerve damage. Stay at 25 mg.

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In detail

Early research. L-methylfolate, 15 mg a day, added to an SSRI that has only half worked, judged after 30 days or more. Go through the doctor, and get vitamin B12 checked first.

Found

About 1 in 6 helped. Four trials, 507 people: L-methylfolate added to an antidepressant lowered depression scores more than the antidepressant alone. In a trial at 15 mg a day, about one extra person responded for every six who took it.

Why

It is the active form of folate the brain uses to build serotonin, dopamine and norepinephrine, with no conversion step needed.

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It can hide a low vitamin B12, so get that checked first. Tell the doctor about any highs. Mild stomach upset in some.

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In detail

Early research. A standardized rhodiola root extract, 340 to 680 mg a day, taken in the morning, for six weeks. Beside an antidepressant only with the doctor.

Found

340 or 680 mg worked. A six-week trial against a placebo: 340 and 680 mg a day both lifted overall depression, sleep and emotional steadiness. Beside sertraline, 0.6 g a day lowered scores more than sertraline alone over twelve weeks. A two-week trial against no supplement: low mood, anxiety and stress fell, and total mood rose.

Why

Rhodiola is an adaptogen: it damps the stress-hormone response and acts on serotonin and dopamine signaling.

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It can feel stimulating: take it in the morning. Dizziness or a dry mouth in some. Tell the doctor about any highs, and before you add it to an antidepressant.

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In detail

Early research. A standardized lemon balm leaf extract, 300 to 600 mg a day, the doses tested in a stress trial, for a few weeks before you judge it. Not with sedatives or alcohol.

Found

Small effect on depression. Trials pooled: lemon balm lowered depression and anxiety scores against placebo, without serious side effects. In a stress test, a single 600 mg dose raised calmness.

Why

Its rosmarinic acid slows the breakdown of GABA, the brain’s main brake, which is where the calm comes from.

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Drowsiness in some: care driving. Not with sedatives, sleeping pills or alcohol. On thyroid medicine, ask first.

In detail

Early research. N-acetylcysteine, 1,000 to 3,000 mg a day in split doses, the range the trials used, for 8 to 24 weeks. Beside the rest of the page, not in place of it.

Found

Small effect, 12 trials. Twelve trials, 904 people: NAC lowered depression scores against placebo. An earlier pooling of five trials found the same on two doctor-rated depression scales.

Why

NAC rebuilds glutathione, the brain’s main antioxidant, and steadies glutamate signaling, two systems that run off course in low mood.

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Stomach upset and nausea, the most common. Rare allergic-type reactions. With asthma, ask first. Not with nitroglycerin: it can drop blood pressure and bring on a headache.

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In detail

Early research. A multi-strain probiotic capsule with lactobacillus and bifidobacterium strains, once a day, for eight weeks. Beside the rest of the page, not in place of it.

Found

d 0.24 on depression. Thirty-four controlled trials: probiotics lowered depression by a small effect. In an eight-week trial of a three-strain capsule, depression scores fell 5.7 points against 1.5 on placebo.

Why

Gut bacteria signal to the brain through immune, hormone and nerve pathways. Topping up the helpful strains may calm the inflammatory side of low mood.

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Wind and bloating for the first week or two. With a weakened immune system, ask the doctor first.

In detail

Early research. Tryptophan, the amino acid the brain makes serotonin from, added to an antidepressant only with the prescriber. The 0.14 to 3 g a day range comes from a different kind of trial, mood studies of tryptophan on its own, not from the add-on trials.

Found

Beat the antidepressant alone. In a network of 192 trials, tryptophan added to an antidepressant beat the antidepressant alone on depression.

Why

It is the raw material for serotonin, and only the fraction not diverted down the kynurenine route reaches it.

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With an SSRI or another serotonin drug it adds to the serotonin load: serotonin syndrome (agitation, fever, sweating, shaking, a fast heart) is the risk, so only with the prescriber. Drowsiness and nausea in some. An outbreak of eosinophilia-myalgia syndrome, a rare inflammatory illness of the muscles, skin and lungs, was linked to tryptophan supplements; impurities from how it was made are the suspected cause.

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In detail

Early research. The oral lavender oil capsule, 80 mg once a day, for ten weeks before you judge it. Not the diffuser oil or the pillow spray.

Found

g 0.43 on depression. Across trials of lavender, depression fell by a small to moderate effect against placebo or no supplement, and anxiety by more. The oral capsule trials ran 80 mg a day for ten weeks.

Why

Its main constituents damp calcium entry at the nerve ending, so less excitatory signal is released.

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Burping, stomach upset and a lavender aftertaste. It may add to the effect of sedatives and sleeping pills.

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In detail

Book the doctor. Take the diary with you: the PHQ-8 scores, the sleep, the drinks, the weeks. Ask what the UK’s NICE guideline offers at your score before you ask for a pill.

Found

odds 0.54 of a diagnosis. In the national survey, men were about half as likely as women to hold a professional diagnosis for the same symptoms. The treatments that got men through the door used role models, plain information about symptoms, services signposted, and content built on responsibility and strength.

Why

Men seek help from a mental-health professional at the same rate as women once they are in front of one. Where they fall behind is in getting there at all. The binding constraint is contact, not willingness.

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In detail

The first-choice antidepressant for most men, on a prescription: sertraline, escitalopram or another SSRI. Sertraline starts at 50 mg a day, and the doctor steps it up if needed. Taken for at least six months once it works.

Found

522 trials; all beat placebo. 522 trials: every one of 21 antidepressants beat placebo in major depression. Six trials pooled: SSRIs raised the risk of trouble reaching orgasm about threefold.

Why

SSRIs block the pump that clears serotonin back into the nerve, so more of it stays working. The mood effect builds over weeks as the brain adapts.

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Boxed warning: antidepressants raised suicidal thoughts and behavior at ages 18 to 24 in short trials. Watch closely in the first months and after any dose change. Sexual side effects: delayed or failed ejaculation, lower drive, erectile trouble. Serotonin syndrome with other serotonin drugs. Bleeding risk with aspirin, NSAIDs or blood thinners. Low blood sodium: headache, confusion, unsteadiness. A heart-rhythm change (QTc) with other risk factors. Angle-closure glaucoma in narrow-angle eyes. Can trigger mania: tell the doctor about any highs. Never stop suddenly.

In detail

If an SSRI does not suit, the doctor switches or adds another. Bupropion when sexual side effects are the problem. Mirtazapine when sleep and appetite have gone. Or an SNRI such as venlafaxine or duloxetine. Bupropion starts at 150 mg and usually goes to 300 mg.

Found

Odds 1.37 to 2.13 over placebo. Across 21 antidepressants, every one beat placebo, some by odds of two to one. Pooled trials of bupropion: a lower risk of sexual side effects than the SSRIs.

Why

They work on different chemistry: bupropion on dopamine and norepinephrine, not serotonin, which is why it spares sex. Mirtazapine blocks receptors that also drive sleep and hunger.

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All carry the same boxed warning on suicidal thoughts at younger ages. Bupropion is ruled out with a seizure disorder, a past eating disorder, an MAOI, or while stopping alcohol or benzodiazepines suddenly. Its seizure risk rises with the dose, and it can raise blood pressure. Mirtazapine: sleepiness and weight gain, so no driving until you know how it hits. Never combine two without the doctor.

In detail

When two antidepressant courses have failed: ask for a course of high-frequency TMS over the left prefrontal cortex. Twenty to thirty sessions, weekday mornings, about six weeks. No anesthetic, no memory loss.

Found

29% responded against 10% on fake. Twenty-nine trials against a fake treatment, 1,371 people. After about thirteen sessions, 29% responded and 19% saw their symptoms clear, against 10% and 5% on the fake. Across 113 trials compared together, high-frequency left TMS tripled the odds of a response.

Why

A coil on the scalp induces a current in the cortex beneath, and repeated pulses shift that region's excitability. The left prefrontal cortex runs under-active in depression, and the course drives it up.

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Scalp pain and headache in the first sessions. Seizure risk is low under standard parameters, and is why it is done in a clinic.

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In detail

For depression that two antidepressants have not touched: a nasal spray given in a certified clinic, on its own or with a daily antidepressant. With acute suicidal thoughts, beside an antidepressant. Twice a week for four weeks, then less often.

Found

Better at day 28. A phase 3 trial, 227 patients who had failed at least two antidepressants: the spray plus a new antidepressant beat the new antidepressant alone at day 28, with gains seen earlier.

Why

Like ketamine, it blocks NMDA glutamate receptors, which sets off fast new connections between brain cells. That is why it works in days where tablets take weeks.

Watch

Boxed warnings: sedation, dissociation, slowed breathing, abuse and misuse, and suicidal thoughts at younger ages. Given only in a certified clinic, watched for at least 2 hours after each dose. Blood pressure rises. No driving until the next day after a night’s sleep. Ruled out with an aneurysm, an arteriovenous malformation, or past bleeding in the brain.

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In detail

In a clinic, for a depression two courses of pills did not touch: an infusion series under a psychiatrist, and a plan for what holds the gain afterwards. Never at home, never as a weekend habit.

Found

effect from day 1 to day 7. Six trials against a placebo, 103 people: an antidepressant effect from day one to day seven. Seventy-nine real-world studies, 2,665 people: a substantial mean effect that holds across repeated treatments.

Why

It blocks NMDA receptors on the inhibitory interneurons first, which lifts the brake on the excitatory cells and sets off a glutamate surge that builds synapses within hours. That is why it works in a day where pills take a month, and why it wears off.

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Dissociation and a blood-pressure rise during the dose, which is why it is observed. Slowed breathing with a high or fast dose. Liver and bile-duct injury with repeated use, so liver tests before a repeat course. Bladder damage and dependence with repeated unsupervised use.

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In detail

For severe depression that has not answered other treatment, or that is dangerous now, as when a man has stopped eating or drinking: a course of ECT under anesthetic, in the hospital.

Found

18 trials; beat medication. Trials pooled: real ECT beat a fake version by a large margin. It beat medication in 18 trials of 1,144 people. It is an effective short-term treatment, probably more so than drugs.

Why

A brief, controlled seizure under full anesthetic resets the brain’s mood circuits faster than any tablet. That speed is why it is kept for the most dangerous lows.

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The risks of a general anesthetic, and memory problems, mostly around the weeks of the course. Decided with a psychiatrist, with the risks laid out in full.