<p>There seem to be multiple studies generally pointing to a delay of clinical antipsychotic action of these drugs, typically between a week and two weeks (<em>e.g.</em>., <a href="https://www.ncbi.nlm.nih.gov/pubmed/22167144" rel="nofollow noreferrer">Zedkova <em>et al</em> (2011)</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076925/" rel="nofollow noreferrer">Mousavi <em>et al</em>. (2013)</a>). However, there is evidence that antipsychotics may start working after a day, or even within a few hours after starting the meds. See for an interesting review <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413955/" rel="nofollow noreferrer">Agid <em>et al</em>. (2006)</a>.</p>

<p>From reading these papers my understanding is that a lot of it depends on where the researcher puts the threshold of <strong><em><a href="https://www.ncbi.nlm.nih.gov/pubmedhealth/aboutcer/" rel="nofollow noreferrer">clinical effectiveness</a></em></strong> and which outcome measure is used to define that effectiveness. </p>

<p><sub><strong>References</strong><br>
<strong>-</strong> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413955/" rel="nofollow noreferrer">Agid <em>et al</em>., <em>J Psychiatry Neurosci</em> (2006); <strong>31</strong>(2): 93–100</a><br>
<strong>-</strong> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076925/" rel="nofollow noreferrer">Mousavi <em>et al</em>., <em>J Res Pharm Pract</em> (2013); <strong>2</strong>(4): 138–44</a><br>
<strong>-</strong> <a href="https://www.ncbi.nlm.nih.gov/pubmed/22167144" rel="nofollow noreferrer">Zedkova <em>et al</em>., <em>Neuro Endocrinol Lett</em> (2011); <strong>32</strong>(5): 667-70</a></sub>  </p>

CC BY-SA 4.0
2018-07-02T13:27:47.683Z
2018-07-02T19:01:03.597Z
2018-07-02T19:01:03.597Z
AliceD
<p>I've been trying to understand the position of <a href="https://en.wikipedia.org/wiki/Steven_Hyman" rel="nofollow noreferrer">Steve Hyman</a> (a former NIMH director), who has been amply quoted in <a href="https://qz.com/1162154/30-years-after-prozac-arrived-we-still-buy-the-lie-that-chemical-imbalances-cause-depression/" rel="nofollow noreferrer">an recent article in Quartz</a>, saying among ohter things that</p>

<blockquote>
  <p>There’s not “an iota of direct evidence” for the theory that a chemical imbalance causes depression.</p>
</blockquote>

<p>I looked into Hyman's papers and I found a fairly cited (~500 in Google Scholar) <a href="https://www.ncbi.nlm.nih.gov/pubmed/8561194" rel="nofollow noreferrer">paper of his some 20 years ago in AJP</a>, co-authored with <a href="https://en.wikipedia.org/wiki/Eric_J._Nestler" rel="nofollow noreferrer">Eric J. Nestler</a>, in which they propose that</p>

<blockquote>
  <p>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.</p>
</blockquote>

<p>The paper further details that</p>

<blockquote>
  <p>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.</p>
  
  <p>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 [...].</p>
</blockquote>

<p>I'm somewhat familiar with the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211759/figure/F2/" rel="nofollow noreferrer">slow, cumulative effect of monoamine antidepressants</a> and with the mechanism of addiction. Hyman and Nestler can be probably be forgiven for not anticipating the <a href="http://time.com/magazine/us/4876068/august-7th-2017-vol-190-no-6-u-s/" rel="nofollow noreferrer">ketamine-as-fast-antidepressant fervor</a> 20 years later. But what I want to ask here is: </p>

<p><strong>What is the evidence that anti-psychotics also work in this delayed manner? Is it uncontroversially so?</strong></p>

CC BY-SA 3.0
2017-12-30T18:35:36.897Z
typical or atypical antipsychotics?
faustus
CC BY-SA 3.0
2017-12-30T18:36:46.623Z
@faustus: they don't particularize their statements to one sub-class of antipsychotics anywhere in the paper, as far as I can tell.
got trolled too much this week
CC BY-SA 3.0
2017-12-30T18:39:34.910Z
are you interested in the first quote, or the answer.re: antipsychotics mechanism of action? the quote is a broader statement about biological psychiatry. it's a position that i share, though i accept that it's not a conventional one.
faustus
CC BY-SA 3.0
2017-12-30T18:55:37.277Z
@faustus: not in this question. It's just for context how I got to read the Hyman and Nestler position paper. The "chemical imbalance" has been derided by other professionals in the field as a [silly, dumbed down version](http://www.psychiatrictimes.com/blogs/nuances-narratives-chemical-imbalance-debate) of the various monoamine hypotheses proposed by researchers. I was trying to understand in exactly what way Hyman rejects that "chemical imbalance". Once a straw man is set up, there are many ways to burn it down...
got trolled too much this week
<neuroscience><abnormal-psychology><psychopharmacology><psychosis>
Do antipsychotics have a delayed onset of action similar to (monoamine) antidepressants?
got trolled too much this week
# Do antipsychotics have a delayed onset of action similar to (monoamine) antidepressants?

(Asked by: username_0 on 2017-12-30)

I've been trying to understand the position of [Steve Hyman](https://en.wikipedia.org/wiki/Steven_Hyman) (a former NIMH director), who has been amply quoted in [an recent article in Quartz](https://qz.com/1162154/30-years-after-prozac-arrived-we-still-buy-the-lie-that-chemical-imbalances-cause-depression/), saying among ohter things that

> There’s not “an iota of direct evidence” for the theory that a chemical imbalance causes depression.

I looked into Hyman's papers and I found a fairly cited (~500 in Google Scholar) [paper of his some 20 years ago in AJP](https://www.ncbi.nlm.nih.gov/pubmed/8561194), co-authored with [Eric J. Nestler](https://en.wikipedia.org/wiki/Eric_J._Nestler), in which they propose that

> 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](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211759/figure/F2/) and with the mechanism of addiction. Hyman and Nestler can be probably be forgiven for not anticipating the [ketamine-as-fast-antidepressant fervor](http://time.com/magazine/us/4876068/august-7th-2017-vol-190-no-6-u-s/) 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?**

**Tags:** neuroscience, abnormal-psychology, psychopharmacology, psychosis

> **Comments:**
> **username_1**: typical or atypical antipsychotics?  
> **username_0**: @username_1: they don't particularize their statements to one sub-class of antipsychotics anywhere in the paper, as far as I can tell.  
> **username_1**: are you interested in the first quote, or the answer.re: antipsychotics mechanism of action? the quote is a broader statement about biological psychiatry. it's a position that i share, though i accept that it's not a conventional one.  
> **username_0**: @username_1: not in this question. It's just for context how I got to read the Hyman and Nestler position paper. The "chemical imbalance" has been derided by other professionals in the field as a [silly, dumbed down version](http://www.psychiatrictimes.com/blogs/nuances-narratives-chemical-imbalance-debate) of the various monoamine hypotheses proposed by researchers. I was trying to understand in exactly what way Hyman rejects that "chemical imbalance". Once a straw man is set up, there are many ways to burn it down...  

---

## 1 answers

### Answer by username_2 on 2018-07-02. Score: 1

There seem to be multiple studies generally pointing to a delay of clinical antipsychotic action of these drugs, typically between a week and two weeks (*e.g.*., [Zedkova *et al* (2011)](https://www.ncbi.nlm.nih.gov/pubmed/22167144) and [Mousavi *et al*. (2013)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076925/)). However, there is evidence that antipsychotics may start working after a day, or even within a few hours after starting the meds. See for an interesting review [Agid *et al*. (2006)](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413955/).

From reading these papers my understanding is that a lot of it depends on where the researcher puts the threshold of ***[clinical effectiveness](https://www.ncbi.nlm.nih.gov/pubmedhealth/aboutcer/)*** and which outcome measure is used to define that effectiveness.

**References**  
**-** [Agid *et al*., *J Psychiatry Neurosci* (2006); **31**(2): 93–100](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1413955/)  
**-** [Mousavi *et al*., *J Res Pharm Pract* (2013); **2**(4): 138–44](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076925/)  
**-** [Zedkova *et al*., *Neuro Endocrinol Lett* (2011); **32**(5): 667-70](https://www.ncbi.nlm.nih.gov/pubmed/22167144)


---

