There’s not “an iota of direct evidence” for the theory that a chemical imbalance causes depression.
drug-induced neural plasticity [...] underlies the long-term actions of psychotropic drugs in the brain [...] Biological investigation in psychiatry has often focused too narrowly on synaptic pharmacology, especially on neurotransmitter turnover and neurotransmitter receptors. A paradigm is presented to help understand the long-term effects of psychotropic drugs, including the latency in onset of their therapeutic actions.
The paper further details that
Acute dosing of the antidepressants produces little in the way of subjective or behavioral effects (other than side effects). Initial doses of the antipsychotic drugs produce subtle motor effects or some degree of sedation, and initial doses of the stimulants produce euphoria and locomotor activation. However, substantial improvement in depressive or psychotic symptoms, or the development of addiction to psychostimulant drugs, occurs only if the drugs are taken at adequate dosage and with adequate frequency and chronicity. For example, depressive symptoms would not be expected to improve if an antidepressant were taken at too low a dose, only occasionally, or for too short a period of time.
We therefore conceptualize antidepressant-induced increases in synaptic serotonin or norepinephrine, antipsychotic- induced blockade of dopamine neurotransmission, and cocaine- and amphetamine-induced increases in synaptic dopamine as initiating events for longerterm changes in neural function. It is the adaptive response of the nervous system to adequate repeated perturbations mediated through these initial targets that produces the therapeutic responses to antidepressants or antipsychotic drugs or, in the case of the psychostimulants, addiction [...].
I'm somewhat familiar with the slow, cumulative effect of monoamine antidepressants and with the mechanism of addiction. Hyman and Nestler can be probably be forgiven for not anticipating the ketamine-as-fast-antidepressant fervor 20 years later. But what I want to ask here is:
What is the evidence that anti-psychotics also work in this delayed manner? Is it uncontroversially so?