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How Do Antidepressants Work?

The simple answer is that we do not know!  Just as Penicillin was discovered by accident and we knew it was a lifesaving antibiotic for very many years before we knew how it worked, the same applies to antidepressant medications.  The first antidepressant, IMIPRAMINE, was discovered in the 1940s dur

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  • The simple answer is that we do not know!  Just as Penicillin was discovered by accident and we knew it was a lifesaving antibiotic for very many years before we knew how it worked, the same applies to antidepressant medications.  The first antidepressant, IMIPRAMINE, was discovered in the 1940s during research on antihistamines. 

    Today, we still have multiple theories on how antidepressants work.  While there are intriguing bits of evidence in the jigsaw, we are still trying to understand exactly what goes wrong in depressive illness and why it is that antidepressant agents make depressed patients better.

    We believe that the chemical pathways in our brain become imbalanced as a result of stress, causing the condition we know as Depressive Illness and all its symptoms.  Put at its most simple, millions of brain cells are repeatedly communicating with multiple other brain cells by shooting chemical messengers from one to the other.  It appears that antidepressant agents make the receiving brain cell more efficient at picking up and acting on the message it receives.  When a chemical message is shot from one brain cell to another, it latches on to receiving areas on the next brain cell, called ‘post-synaptic receptors’.  (A synapse is the space between two nerve cells and it is across this space that the chemical message is shot from one brain cell to another;  post-synaptic receptors are the receiving areas beyond the synapse space.)  

    We believe that antidepressants also act by altering the feedback messages between one brain cell and another, so that the transmitting brain cell starts to send more frequent messages to the receiving brain cell and its post synaptic receptors.  Some antidepressants also prolong the life of the chemical messenger, although we now believe this action is not as important as we once thought.  The theories of how antidepressants work and indeed the theories about the problem in depressive illness itself, are continuously being refined. 

    Each new development in science requires modification of our theories.  For example, within the space of a few years it was realised that there were not three different types of post-synaptic receptors, but in fact approximately 15 types of post-synaptic receptors, all carrying out different functions.  The human brain is an immensely complicated structure and we are only beginning to understand the tiniest bits about it.

    Important Disclaimer:  This site is medical information only and is not to be taken as diagnosis, advice or treatment, which can only be decided by your own doctor.

    Clinically reviewed. This article was written and reviewed by the clinical team at the Australian Suicide Prevention Foundation.

    Important: This information is general guidance and does not replace professional medical advice. If you are in crisis, please call Lifeline on 13 11 14 or 000 for immediate danger.