Prevalence, clinical features and treatment of depression in Parkinson’s disease: An update

Table 2 Classification, mechanism of action and dosage range of antidepressants

Class	Mechanism of action	Generic name (trade name)	Dose range (mg/d)
Older antidepressants
Mixed serotonin and norepinephrine reuptake inhibitors
First-generation tricyclic antidepressants	Inhibit neuronal reuptake of norepinephrine and serotonin	Amitriptyline (elavil) Clomipramine (anafranil) Doxepin (adapin) Imipramine (tofranil) Trimipramine (surmontil) Protriptyline (vivactil) Lofepramine	100-300 100-250 100-300 50-300 100-300 75-200 15-60
Second-generation tricyclic antidepressants	Inhibit neuronal reuptake of norepinephrine and serotonin	Desipramine (norpramin) Nortriptyline (pamelor)	100-300 50-150
Tetracyclic antidepressants	Inhibit neuronal reuptake of norepinephrine and serotonin	Maprotiline (ludiomil)	100-200
		Amoxapine (asendin)	50-300
Heterocyclic agents Triazolopyridines	Mixed serotonin effects: Serotonin (5-HT2A) receptor blockade with serotonin reuptake inhibition	Trazodone (desyrel)	150-400
Monoamine oxidase inhibitors	Nonselective inhibitor of monoamine oxidase A and B	Phenelzine (nardil) Tranylcypromine (parnate) Selegiline (eldepryl)	60-90 20-60 5-10
Newer antidepressants
Selective serotonin reuptake inhibitors	Selectively inhibit the reuptake of 5HT at the presynaptic neuronal membrane. Sertraline also markedly inhibits dopamine reuptake	Fluoxetine (prozac) Fluvoxamine (luvox) Paroxetine (paxil) Sertraline (zoloft) Citalopram (celexa) Escitalopram (lexapro)	20-60 100-300 20-50 50-200 20-40 5-20
Serotonin and noradrenaline reuptake Inhibitors	Potent inhibitors of 5HT and norepinephrine uptake; weak inhibitors of dopamine reuptake	Venlafaxine (effexor) Milnacipran (savella) Duloxetine (cymbalta)	75-350 12.5-100 60
Norepinephrine reuptake inhibitors	Noradrenaline reuptake inhibitor. Inhibits norepinephrine reuptake without inhibiting serotonin reuptake	Viloxazine Reboxetine (edronax) Atomoxetine (strattera)	150-300 4-8 40-80
Reversible inhibitors of monoamine oxidase A	Selective, reversible inhibitors of monoamine oxidase A: resulting in increased concentrations of NE, 5-HT, and dopamine in synapse	Moclobemide Brofaromine	300-600 75-150
5HT2 receptor antagonists/reuptake inhibitor serotonin modulators	Mixed serotonin effects. Inhibition of the reuptake of serotonin and selective postsynaptic 5-HT2A blockade	Nefazodone (serzone) Desvenlafaxine (pristiq) Ritanserin	300-600 50 mg once daily 5-10
5HT1a receptor agonists	Partial agonist of serotonin 5-HT1a	Gepirone, ipsapirone, tandospirone, felsinoxan
α2-noradrenergic antagonists	Complex action on serotonin and noradrenaline via Serotonin (5-HT2A and 2C) receptor blockade and presynaptic α2-receptor blockade	Mirtazapine (remeron)	15-45
GABA-mimetics	GABAA and GABAB receptor agonists	Fengabine	900-1800
Dopamine reuptake inhibitors	Increases activity of norepinephrine and dopamine only; no significant effect on serotonin	Buproprion (wellbutrin)	200-450
Melatonin receptor agonists	Melatonin MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist	Agomelatine (valdoxan)	25-50
Herbal remedy: Hypericumperforatum/ St. John’s wort	Unclear: inhibits the reuptake of several neurotransmitters, including 5HT, NE, dopamine, and γ-aminobutyric acid	Hypericum perforatum	300-900

Clomipramine, nefazodone and venlafaxine are potent non-selective serotonin reuptake inhibitors. Citalopram S-enantiomer, escitalopram, is the most active isomer and is a more potent and more selective serotonin reuptake inhibitor than citalopram. Extracts of Hypericum perforatum (St. John’s Wort) are used in many countries to treat depressive disorders. GABA: Gamma aminobutyric acid; NE: Norepinephrine; 5HT: 5-hydroxytryptamine.