Cushing, the father of neurosurgery, noted that pituitary gland problems often cause mental health disorders. He wondered whether the depression and anxiety he observed in patients with pituitary disorders were caused by hormonal abnormalities, the physical tumor itself, or both. Mid 20th century An important point in modern history of biological psychiatry was the discovery of modern antipsychotic and antidepressant drugs. Chlorpromazine (also known as Thorazine), an antipsychotic, was first synthesized in 1950. In 1952, iproniazid, a drug being trialed against tuberculosis, was serendipitously discovered to have anti-depressant effects, leading to the development of MAOIs as the first class of antidepressants. In 1959 imipramine, the first tricyclic antidepressant, was developed. Research into the action of these drugs led to the first modern biological theory of mental health disorders called the catecholamine theory, later broadened to the monoamine theory, which included serotonin. These were popularly called the "chemical imbalance" theory of mental health disorders. Late 20th century Starting with fluoxetine (marketed as Prozac) in 1988, a series of monoamine-based antidepressant medications belonging to the class of selective serotonin reuptake inhibitors were approved. These were no more effective than earlier antidepressants, but generally had fewer side effects. Most operate on the same principle, which is modulation of monoamines (neurotransmitters) in the neuronal synapse. Some drugs modulate a single neurotransmitter (typically serotonin). Others affect multiple neurotransmitters, called dual action or multiple action drugs. They are no more effective clinically than single action versions. That most antidepressants invoke the same biochemical method of action may explain why they are each similarly effective in rough terms. Recent research indicates antidepressants often work but are less effective than previously thought. Problems with catecholamine/monoamine hypotheses The monoamine hypothesis was compelling, especially based on apparently successful clinical results with early antidepressant drugs, but even at the time there were discrepant findings. Only a minority of patients given the serotonin-depleting drug reserpine became depressed; in fact reserpine even acted as an antidepressant in many cases. This was inconsistent with the initial monoamine theory which said depression was caused by neurotransmitter deficiency. Another problem was the time lag between antidepressant biological action and therapeutic benefit. Studies showed the neurotransmitter changes occurred within hours, yet therapeutic benefit took weeks. To explain these behaviors, more recent modifications of the monoamine theory describe a synaptic adaptation process which takes place over several weeks. Yet this alone does not appear to explain all of