You can’t just snap out of it. You’ve tried. You’ve pushed through. But the heaviness doesn’t lift. It’s not laziness or weakness. It’s not just sadness. It’s depression – and it changes your brain, your body, and your sense of self.

Let’s unpack what’s actually happening beneath the surface – and why there’s more hope than you’ve been led to believe.

Depression Isn’t Just a Mood. It’s a Brain State.

Depression is a complex brain-body condition that alters the way you think, feel, move, and even remember. It isn’t caused by one thing. It’s the result of a multi-system imbalance – chemical, hormonal, inflammatory, and neurological.

Modern neuroscience confirms that depression affects key regions in the brain:

• The prefrontal cortex (responsible for rational thinking and decision-making) slows down.
• The amygdala (emotional alarm system) becomes hyperactive.
• The hippocampus (memory and mood regulation) often shrinks, especially in long-term depression.

It’s not all in your head. It’s in your nervous system. It’s in your cells. And now, we understand it better than ever.

The Chemical Conversations: Neurotransmitters

You’ve probably heard of serotonin, often labelled the “feel-good” chemical. But it does more than lift mood. It regulates sleep, digestion, appetite, and pain. Low serotonin is linked to anxiety and insomnia, not just sadness.

SSRIs (Selective Serotonin Reuptake Inhibitors) are the most commonly prescribed antidepressants. They work by increasing serotonin levels in the brain, but they’re not the only option.

Other medication classes include:

• SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors)
• NDRIs (targeting dopamine and norepinephrine)
• Atypical antidepressants like bupropion or mirtazapine
• MAOIs, used less frequently due to dietary restrictions but sometimes life-changing
• And in treatment-resistant cases: Ketamine, esketamine nasal spray, or psilocybin-assisted therapy in clinical trials

New studies, including a 2024 review in The Lancet Psychiatry, show that personalised approaches, matching medication type to individual biochemistry, can significantly improve outcomes.

Dopamine: The Motivation Molecule

While serotonin helps regulate mood, dopamine drives pleasure, reward, and motivation. If you feel flat, numb, or like nothing brings you joy anymore — that’s likely dopamine depletion.

Low dopamine can show up as:

• Lack of motivation to get out of bed
• Loss of interest in things you used to love
• Emotional blunting
• Cravings or compulsive behaviours (as a way to “self-medicate”)

Some newer treatment plans specifically target dopamine and norepinephrine for this reason.

Inflammation and the Brain

One of the most exciting developments in depression research? Inflammation. Studies now show that chronic low-grade inflammation can drive symptoms of depression, especially in people who don’t respond well to standard antidepressants.

A 2023 study in Molecular Psychiatry found that people with elevated inflammatory markers (like CRP and cytokines) often experience more fatigue, fog, and emotional numbness.

Causes of this inflammation include:

• Poor gut health
• Chronic stress
• Autoimmune conditions
• Food sensitivities
• Trauma

That’s why anti-inflammatory approaches – like eliminating trigger foods, improving sleep, and addressing trauma – are now integrated into many holistic depression treatment plans.

Supplements With Emerging Evidence

These are not miracle cures, but they’re well-supported by data and widely used alongside therapy or medication:

Saffron extract
Multiple meta analyses show it rivals SSRIs in mild to moderate depression at doses around 30 mg daily.

Omega 3 (EPA heavy)
Anti inflammatory and mood stabilising. Aim for 1000 to 2000 mg EPA daily.

Magnesium glycinate or threonate
Calms the nervous system and supports sleep. Deficiency is very common and linked to low mood.

Vitamin D3
Low levels are strongly correlated with higher rates of depression. Supplementing can improve both mood and energy.

Ashwagandha KSM 66
Helps reduce cortisol and emotional reactivity. Also supports sleep quality and resilience.

L Theanine
Supports focus and reduces the physical tension that often comes with anxiety.

5 HTP
A serotonin precursor that may lift mood. Needs medical guidance, especially if combined with SSRIs.

Creatine
Traditionally seen as a sports supplement, but now studied for mood. It supports brain energy metabolism, enhances antidepressant response, and shows early benefits for both depression and anxiety.

St John’s Wort
One of the most researched herbal antidepressants. Dozens of trials show it outperforms placebo and rivals SSRIs in mild to moderate depression. Very effective, but it strongly interacts with many medications, including birth control and antidepressants, so medical supervision is essential.

SAMe (S Adenosyl Methionine)
A natural compound involved in neurotransmitter synthesis. Shown in trials to be as effective as prescription antidepressants at higher doses (800–1600 mg daily). Particularly useful when folate metabolism is impaired.

Rhodiola Rosea
An adaptogen that reduces fatigue and boosts resilience to stress. Several trials show improvements in mild to moderate depression and burnout related mood dips.

N Acetylcysteine (NAC)
A powerful antioxidant that modulates glutamate and inflammation. Large meta analyses show it reduces depressive symptoms, especially in people with treatment resistant depression or co existing anxiety.

Always consult a professional before combining supplements with antidepressants.

Movement Is Medicine

When your brain says “don’t move,” move anyway – gently. Consistent, low-impact movement (like walking, yoga, or swimming) stimulates dopamine and BDNF (brain-derived neurotrophic factor), which helps repair and regrow neurons damaged by chronic stress.

A 2023 review in JAMA Psychiatry concluded that movement was equally effective as medication for mild-to-moderate depression when done regularly (3–5 times/week, 30 minutes).

The hard part? Starting. The key is micro-movement. Stretching. Getting outside. Rolling your shoulders. Start there.

Therapy Still Matters

Even with all this brain science, therapy is key – especially trauma-informed approaches. Here’s what’s working right now:

CBT (Cognitive Behavioural Therapy) for rewiring thought patterns

EMDR for trauma-linked depression

Internal Family Systems (IFS) for emotional integration

Somatic therapy for body-stored grief and stress

Psychedelic-assisted therapy (in clinical trials) for treatment-resistant depression

Also rising: peer communities, nervous system regulation practices, and breathwork.

Where to Turn

NHS or GP: First step if you’re in the UK and suspect depression

Mind (UK): mind.org.uk – Support and guides

Calm My Mind’s Directory (coming soon): Curated professionals, retreats, and tools

Therapists specialising in trauma, somatic work, or nervous system health

Private testing for intolerances, inflammation, gut health, and hormone imbalances

The Calm Conclusion

Depression isn’t a flaw. It’s not weakness. It’s a signal that something real is out of balance – physically, mentally, emotionally. And you’re allowed to seek support for that.

You don’t have to “fix” it all at once. Start where you are. With one supplement. One walk. One honest conversation.

Healing is a system upgrade, not a personality change. And yes, you can find your way back.