Along with nutrient imbalances, the Pfeiffer Center has found that an overload of copper and toxic substances also contributes to mental problems such as bipolar disorder. Depressives with high copper levels usually have a history of hyperactivity, tinnitus and skin sensitivity to metals. Women with this condition often have significant premenstrual syndrome (PMS) and are prone to heightened depression during other hormonal events such as childbirth and menopause. Symptoms often worsen when given oestrogen or multiple vitamins. Treatment needs to release excess copper from tissues, promote copper excretion and stimulate metallothionein (a metal-binding protein).

Toxic substances capable of producing depression include lead, cadmium, mercury, and a wide variety of organic and inorganic chemicals. Overloads of this type can produce a sudden, prolonged bout of depression without apparent reason even in those without a prior history of depression. Treatments vary according to the toxic substance involved. Heavy-metal overloads can be corrected quickly by in-hospital chelation, though care must be exercised to avoid flooding the kidneys with toxins during the early stages of treatment. A long-term ‘cure’ of a toxic overload often requires high-dose antioxidants as well as lifestyle adjustments to help the individual avoid toxic triggers.