Mechanism of action and pharmacodynamics

Dothiepin is a tricyclic antidepressant. It acts by promoting the effectiveness of several amines (dopamine, norepinephrine, and 5-hydroxytryptamine, which is also known as 5HT and serotonin). It functions by inhibiting their reuptake at the terminals of nerve cells, thus leading to their prolonged presence at the synaptic cleft and an increased effect on the neuron.(1) The reuptake pumps for the above amines are responsible for reducing the concentration of these amines. Dothiepin works by blocking the pumps.

According to the amine hypothesis, a decreased concentration of the amines and the resulting decrease in amine dependant synaptic transmission is associated with depression, therefore an increase in the above would help relieve the symptoms of depression. (2)

Dothiepin has other actions as well. It reduces norepinephrine induced CAMP formation in the brain, as well as inhibiting the uptake of 5HT into platelets. It also has some anticholinergic and antihistaminic activity.(3)

Dothiepin begins to take effect after approximately 2-3 weeks. Us

Tryptophan can cause increased agitation, restlessness and g. i. distress. Other antidepressants should also be avoided, as fluoxetine greatly reduces their clearance. Lithium interacts with fluoxetine, although unpredictably. In some cases Lithium levels have been seen to fall, in some to rise, even to toxic levels. CNS active drugs warrant caution when used concurrently with fluoxetine, as it will reduce their clearance, and increase their effects. (3)

ual daily doses of Dothiepin range from 75mg to 200mg in the more severe cases. (2)

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