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Posted: October 2nd, 2024
Antidepressant Drugs: Types, Effects and Developments
Introduction:
Depression is one of the parts of mental disorder which is affecting millions of people worldwide. [6] The logical analytical approach used in clinical and forensic toxicology for the identification of one or more Antidepressant Drugs as a cause of intoxication is largely based on both simple and fast screening methods which cover their extraction and identification including detection of their possible metabolites is been tried to reviewed.
Antidepressant: Types & Functions
Antidepressant drugs cover many varieties of drugs having different modes of actions like [16] etc.
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Adverse effects
Antidepressants are supposed to increase the risk of suicidal thinking and behavior in children accompanying other disorders like depressive and psychiatric disorders. [17] [18] [19] The European Medicines Agency showed warning on the use of Antidepressants which might be increased the risk of suicidal behavior in children and adolescents. [31] TCAs and MAOIs can produce similar kind of side effects like Tachycardia, blurred vision, urinary retention, cardiovascular effects , hypotension, respiratory depression, coma etc. [4] Thus, these drugs may be responsible for the fatality and intoxication and can produce severe effects. Also their growing rate all over the world may show threatening effects which is the matter of global concern. Thus, it’s increasing prescription rate and adverse effects resulting in a growing interest for determination methods in the Clinical and Forensic field.
Biological Samples use for the Screening of Antidepressant Drugs
Biological samples are the basic requirement of Forensic and Clinical Toxicology as it solve several related questions which make basis of judgement, consultation and expertise for the above two fields. The matrices generally encountered for analysis are urine [34], hair, nails, vitrous humour etc.
The most important biosample used for analytical purposes is Blood. It is a liquid connective tissue of the body composed of different kinds of blood cells suspended in a fluid called plasma. Blood (plasma, serum) is one of the best choices for quantitative and qualitative measurements of drugs of interest because pharmacological or toxicological effects correlate more effectively with their concentrations in blood. [42]
Another important biological sample is Urine which is a widely used specimen employed for screening, identification and testing of unknown drugs, forms in high amount, readily available, easy to collect and contains much useful information about the major metabolic functions of the body. [43]
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Taking Forensic concept in postmortem cases if the positive finding of drug occurs in urine shows that the detected substance or it’s parent compound might be present in the body some time before death [48]
A next alternative to the blood and urine specimen found is Oral fluid for their applications in therapeutic and toxicological drug monitoring [54]
When analytical studies get concern with long duration of exposure to the detection window Hair could be as a best biological matrix for the identification and analysis of drugs. It is supposed that drugs or chemicals enter in to hair by passive diffusion from blood capillaries into growing cells and the mechanisms of substance incorporation, analytical methods, result interpretation and practical applications of hair analysis has been well reviewed showing practical utility of hair analysis. [62]
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Except from all the above given matrices one very precise and rarely encountered biological sample is Vitreous Humor. It’s a fluid found between the lens and retina of the eye proved to be the best choice for analytical examinations as it is relatively well isolated and protected from putrefaction. Two different fatality cases were reported where the extraction of drugs is done from Vitreous humor. One case has been reported of citalopram fatality where the extraction of drug is done from Vitreous humor yeilding concentration of citalopram (SSRI) less than 0.04mg/L and in second case venlafaxine fatality is reported where postmortem analysis revealed the concentrations of Fluoxetine (SSRI) and it’s metabolite Norfluoxetine as 5.2 mg/l and 2.2mg/l respectively. [64]
Other than these specimens, body tissues like liver [71], cerebrospinal fluid etc. canalso encounter for toxic and therapeutic drug monitoring biological matrices.
Techniques for Sample Preparation
Several methods have been published for the determination of one or more antidepressants in biological fluids for therapeutic monitoring or for toxicological purposes. For making biological samples suitable for analytical purposes some treatments should be given to overcome the matrix effects such that the other materials should not interfere with the analytical separation that is the extractability of the analytes in the sample inturn the results of the analysis. [96] These kinds of techniques are rapidly gaining acceptance in bioanalytical applications to reduce both time and labor required to produce bioanalytical results. Thus we can say that these methods give a high selectivity and sensitivity over a wide dynamic range and contribute in formulating very fine detection techniques.
Some Commonly Prescribed New Generation Antidepressant Drugs and their Metabolites
Several new antidepressants that inhibit the Serotonin (SERT) and Norepinephrine transporters (NET) have been consistently use for therapeutic purposes. [108] are showing below.
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Sertraline is an effective and highly utilized SSRIs group of drug and “it’s principle metabolite is desmethylsertraline.” [41]
Another SSRIs group of Antidepressant drug, Fluoxetine has been used worldwide in the therapy of major depression. (3) “It is primarily metabolized via N-demethylation by the [117]
Citalopram is a selective and potent serotonin reuptake inhibitor. [78]
Another very important group of Antidepressant drug is SNRIs which includes drugs like Venlafaxine which inhibits serotonin, noradrenaline, and to a lesser extent dopamine reuptake. [39]
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In the majority of published analytical methods for determination of Antidepressant drugs, gas chromatography and high-performance liquid chromatography, in combination to different kinds of colums operating under different separation conditions, mobile phases and detectors has been used. These were tried to review in the table given below. With high-performance liquid chromatography the analysis is done by using different kinds of detectors like Fluorescence detector, UV detector, Mass detectors etc. For ex. a high-performance liquid chromatographic method is described for the determination of serotonin and norepinephrine reuptake inhibitor (SNRI) in human plasma where Fluorescence detector was used. [140] A survey of most recent multiresidue analytical methods developed for the determination of different kinds of Antidepressant drugs in different types of biological test matrices with their specific cleanup procedures including the choice of mobile phase, stationary phase, detector system and validation data is summarized in the tabular form below.
TABLE
|
Analytical Method |
Matrix |
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Extraction method |
Column |
Mobile phase |
Detector system Who’s Behind My Essays?You’re in good hands with degree-holding pros—many rocking Master’s or higher—who’ve crushed our tough vetting tests in writing and their fields. They’re your partners in this, hitting tight deadlines and academic standards with ease, all while tailoring every essay to your exact needs. No matter the topic, they’ve got the chops to make it stellar. |
Limit of detection/quantification (ng/L)/ analytical range |
References |
|
LC-MS |
Plasma Is My Paper Original?100%—we promise! Every paper’s written fresh from scratch—no AI, no copying—just solid research and proper citations from our expert writers. You can even request a plagiarism report to see it’s 95%+ unique, giving you total confidence it’s submission-ready and one-of-a-kind. |
Fluoxetine and norfluoxetine |
Automated SPE |
XTerra MS C18 |
Formic acid in methanol and water Can You Do Any Citation Style?Yep—APA, Turabian, IEEE, Chicago, MLA, whatever you throw at us! Our writers nail every detail of your chosen style, matching your guidelines down to the last comma and period. It’s all about making sure your paper fits academic expectations perfectly, no sweat. |
Triple stage, ESI, positive mode, SRM |
Fluoxetine and norfluoxetine, m/z 310.3 and 296.2 resp.Linearity,0.5-50ng/mL for both the analyte. |
81 |
|
LC-MS Can I Adjust Instructions Later?Absolutely—life happens, and we’re flexible! Chat with your writer anytime through our system to update details, tweak the focus, or add new requirements, and they’ll pivot fast to keep your paper on point. It’s all about making sure the final draft is exactly what you need, no stress involved. |
Plasma |
Fluoxetine and norfluoxetine |
On-line extraction using column switching |
Oasis HLB and Discovery HS C18 How Do I Get Started?It’s super easy—order online with a few clicks, then track progress with drafts as your writer works their magic. Once it’s done, download it from your account, give it a once-over, and release payment only when you’re thrilled with the result. It’s fast, affordable, and built with students like you in mind! |
Formic acid in acetonitrile and water |
ESI, positive mode, SIM |
LOQ,25ng/Ml for both . |
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|
LC- MS |
Hair |
citalopram and it’s metabolites |
liquid/liquid extraction |
narrow bore C18 Can You Handle Complex Subjects?For sure! Our writers with advanced degrees dive into any topic—think quantum physics or medieval lit—with deep research and clear, sharp writing. They’ll tailor it to your academic level, ensuring it’s thorough yet easy to follow, no matter how tricky the subject gets. |
_ |
Tandem mass spectrometre |
LOQ 25 pg/mg |
61 |
|
HPLC How Do You Meet Prof Standards?We stick to your rubric like glue—nailing the structure, depth, and tone your professor wants—then polish it with edits for that extra shine. Our writers know what profs look for, and we double-check every detail to make sure it’s submission-ready and grade-worthy. |
Plasma |
Venlafaxine,desmethylvenlafaxine, N,O-didesmethylvenlafaxine |
liquid-liquid extraction |
Thermo BDS HYPERSIL C18 What’s Your Editing Like?Send us your draft and tell us your goals—we’ll refine it, tightening arguments and boosting clarity while keeping your unique voice intact. Our editors work fast, delivering pro-level results that make your paper pop, whether it’s a light touch-up or a deeper rework. |
water (ammonium acetate: 30mmol/l, formic acid 2.6mmol/l, trifluoroacetic acid 0.13mmol/l) and acetonitrile (60:40, V/V) |
MS/ESI |
LOD were 0.4, 0.2, 0.3, and 0.2ng/ml for VEN, ODV, NDV and DDV resp. |
134 |
|
HPLC Can You Pick My Topic?Yes—we’ve got your back! We’ll brainstorm fresh, workable ideas tailored to your assignment, picking ones that spark interest and fit the scope. You choose the winner, and we’ll turn it into a standout paper that’s all yours. |
Plasma |
Venlafaxine ,O-di desmethylvenlafaxine |
solid-phase extraction with C1 cartridges |
reversed-phase column -C8 |
75% aqueous phosphate buffer containing triethylamine and 25% acetonitrile |
Fluorescence detector |
LOQ 1.0ngmL−1 and LOD 0.3ngmL−1 Do You Do Quick Revisions?Yep—need changes fast? We’ll jump on your paper and polish it up in hours, fixing whatever needs tweaking so it’s ready to submit with zero stress. Just let us know what’s off, and we’ll make it right, pronto. |
39 |
|
GC-MS |
oral fluid |
amitryptiline, paroxetine and sertraline |
solid-phase extraction with Bond elute column {Acid compounds were eluted with acetone while basic and neutral compounds with dichloromethane:isopropanol:ammonium (80:20:2, v/v/v)} |
methylsilicone capillary column Can You Outline First?Sure thing! We’ll whip up a clear outline to map out your paper’s flow—key points, structure, all of it—so you can sign off before we dive in. It’s a handy way to keep everything aligned with your vision from the start. |
Carrier gas He, Flow rate 0.8ml/min |
selected-ion-monitoring (SIM) mode. |
Between0.9 and 44.2ng/ml (LOQ) |
55 |
|
HPLC |
Plasma |
citalopram and it’s metabolites |
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reversed-phase column -C18 |
40% acetonitrile: 60% aqueous tetramethylammonium perchlorate |
Fluorescence detection at 300 nm, exciting at 238 nm |
(LOQ) 1.5 ng mL−1 citalopram and desmethylcitalopram , 2.0 ng mL−1 for didesmethylcitalopram |
124 |
|
HPLC |
Plasma |
fluvoxamine, paroxetine, sertraline, fluoxetine, citalopram, mirtazapine, milnacipram, venlafaxine, desmethylcitalopram, didesmethylcitalopram, norfluoxetine, O-desmethyl venlafaxine, desmethylmirtazapine |
liquid-liquid extraction |
Symmetry C8 How Do You Manage Big Projects?We tackle each chunk with precision, keeping quality consistent and deadlines on track from start to finish. Whether it’s a dissertation or a multi-part essay, we stay in sync with you, delivering top-notch work every step of the way. |
acetonitrile-phosphate buffer 10 mM |
UV (230 nm and 290 nm) |
LOD, 25 to 500 ng/mL (100-2000 ng/mL for venlafaxine and its metabolite), |
142 |
|
HPLC-MS Do You Follow Global Academic Rules?Yes—we’ve got it down! Our writers switch seamlessly between UK, US, Australian, or any other standards, matching your school’s exact expectations. Your paper will feel native to your system, polished and ready for wherever you’re studying. |
Blood |
fluoxetine, paroxetine, sertraline, fluvoxamine, Citalopram, norfluoxetine, desmethylcitalopram, didesmethylcitalopram, desmethylvenlafaxine, and desmethylmirtazapine |
liquid-liquid extraction. |
XTerra RP18 column |
Acetonitrile and ammonium formate buffer (4 mmol/L) What is a progressive delivery and how does it work?Progressive delivery is a cool option where we send your paper in chunks—perfect for big projects like theses or dissertations. You can even pay for it in installments. It’s just 10% extra on your order price, but the perks are worth it. You’ll stay in closer touch with your writer and can give feedback on each part before they move to the next. That way, you’re in the driver’s seat, making sure everything lines up with what you need. It saves time too—your writer can tweak things based on your notes without having to redo huge sections later. |
Tandem mass spectrometre |
LOD, 5-500 ng/mL (20-2000 ng/mL for venlafaxine and desmethylvenlafaxine) and |
143 |
|
HPLC I received some comments from my teacher. Can you help me with them?Absolutely! If your teacher’s got feedback, you can request a free revision within 7 days of approving your paper—just hit the revision request button on your personal order page. Want a different writer to take a crack at it? You can ask for that too, though we might need an extra 12 hours to line someone up. After that 7-day window, free revisions wrap up, but you can still go for a paid minor or major revision (details are on your order page). What if I’m not satisfied with my order? If your paper needs some tweaks, you’ve got that free 7-day revision window after approval—just use the “Revision” button on your page. Once those 7 days are up, paid revision options kick in, and the cost depends on how much needs fixing. Chat with our support team to figure out the best way forward. If you feel the writer missed the mark on your instructions and the quality’s off, let us know—we’ll dig in and sort it out. If revisions don’t cut it, you can ask for a refund. Our dispute team will look into it and figure out what we can offer. Check out our money-back guarantee page for the full scoop. |
Serum |
fluvoxamine, milnacipran, paroxetine, sertraline, fluoxetine, citalopram, venlafaxine, desmethylcitalopram, didesmethylcitalopram and norfluoxetine |
liquid-liquid extraction. |
Beckman C18 reversed-phase column |
(50%, v/v) acetonitrile in a sodium phosphate buffer (0.05 M with pH 3.8) |
UV (200.4 nm) |
15 ng/ml -fluoxetine, 25 ng/ml-venlafaxine, norfluoxetine, citalopram and its metabolites, 40 ng/ml- sertraline, 50 ng/ml-fluvoxamine |
127 |
|
Capillary Liquid chromatography |
Plasma |
citalopram, fluoxetine, paroxetine and their metabolites |
reversed-phase C8 SPE |
Kromasil, C18 |
acetonitrile-45 mM ammonium formate (25:75, v/v). |
UV |
LOQ between 0.05 to 0.26 μM |
42 |
|
HPLC |
Plasma |
fluoxetine and norfluoxetine |
Sample treated with acetonitrile and isolated supernatants were directly injected |
Discovery C18 |
0.1% formic acid in water and acetonitrile (40: 60) |
ESI- Tandem Mass spectrometre, (m/z 310 → m/z 44.3 for fluoxetine, m/z 296 → m/z 134 for norfluoxetine) |
LOD, fluoxetine, 0.02 ng/mL and 0.03 ng/mL, norfluoxetine |
95 |
|
RP-HPLC |
Serum |
Sertraline |
liquid- liquid extraction. |
cyano column |
63:37 (v/v) methanol-sodium phosphate buffer (0.05M) containing 2mLL−1 triethylamine |
Fluorescence detector |
LOQ up to 2ngmL− |
111 |
|
LC-MS/MS |
plasma |
Sertraline, N-desmethyl sertraline |
liquid-liquid extraction |
Betasil C8 column |
750 mL methanol + 250 mL deionized water + 2.5 mL, 1.0 M ammonium trifluoroacetate. |
tandem mass spectrometry |
SER, NDS were were m/z 306.2→159.0, 292.1→159.0, resp. |
12 |
|
LC-MS/MS |
Plasma |
venlafaxine (VEN) and O-desmethyl venlafaxine (ODV) |
SPE |
Betasil C18 column |
isocratic |
tandem mass spectrometry |
m/z 278.27→121.11 for VEN, m/z 264.28→107.10 for ODV |
144 |
|
RP-HPLC |
Pharmaceutical formulations. |
Olanzapine, fluoxetine. |
_ |
Inertsil C18 reversed phase column |
40:30:30 (v/v/v) mixture of 9.5mM sodium dihydrogen phosphate, acetonitrile & methanol |
UV |
LOQ, 0.005 & 0.001μgmL−1 for olanzapine and fluoxetine resp. |
145 |
|
HPLC-MS-MS |
Plasma |
Citalopram, fluvoxamine and paroxetine |
On-line SPE with column switching.(Oasis/HLB) |
Oasis HLB and Symmetry C18 |
Formic acid in water and acetonitrile |
Triple stage, APCI, positive mode, SRM |
LLOQ, 20 microg/ L for citalopram & fluvoxamine and 10 microg/L/ for paroxetine. LOD, 5 microg/ L for all |
131 |
|
LC-MS(/MS) |
Plasma |
Citalopram |
LLE |
Hypersil BDS C8 |
Aqueous ammonium formate and acetonitrile |
ESI, positive mode, SIM |
Analytical range, Citalopram 0.50-250ng/mL |
146 |
|
LC-MS(/MS) |
Plasma |
Fluoxetine and norfluoxetine |
LLE |
Lichrospher 100 RP-8 E |
Aqueous ammonium formate and acetonitrile |
ESI, positive mode, SIM |
Analytical range, Fluoxetine 2.5-250ng/mL, norfluoxetine 10-250ng/mL |
147 |
|
LC-MS(/MS) |
Plasma |
Sertraline |
SPE |
Beta Basic C-8 |
Aqueous ammonium formate and acetonitrile |
Triple stage, ESI, positive mode, SRM |
Analytical range, Sertraline 0.5-60.0ng/mL |
148 |
|
LC-MS(/MS) |
Plasma |
Fluoxetine |
Stir bar sorptive extraction |
Luna C18 |
Aqueous ammonium acetate and methanol |
ESI, positive mode, SIM |
Analytical range, Fluoxetine 10-500ng/mL |
74 |
|
LC-MS(/MS) |
Plasma |
Fluoxetine, citalopram, paroxetine and venlafaxine |
SPE |
C18 |
Aqueous ammonium acetate and acetonitrile |
ESI, positive mode, SIM |
Analytical range, Fluoxetine, citalopram, paroxetine, venlafaxine 5.0-1,000.0ng/mL |
149 |
|
LC-MS |
Plasma |
Citalopram |
liquid-liquid extraction |
Hypersil BDS C8 microbore column |
10mM ammonium formate- formic acid and acetonitrile (30:70 v/v) |
Positive electrospray ionization with selected ion monitoring mode. |
m/z- 325 citalopram, m/z- 281 imipramine, LOQ- 0.50 ng/ml. |
75 |
|
HPLC-MS/ ESI |
Plasma |
Fluoxetine, citalopram, paroxetine and venlafaxine |
SPE |
Macherey- NA Gel C18 column |
Water (formic acid 0.6%, ammonium acetate 30mmol/l) and acetonitrile, 35:65 (v/v) |
Electron spray ionization |
LOD, Fluoxetine 0.5, citalopram 0.3, paroxetine 0.3 and venlafaxine 0.1 ng/ml |
80 |
|
HPLC |
Plasma |
Fluoxetine and Norfluoxetine |
liquid-liquid extraction |
Reverse phase C18 column |
Phosphate buffer and acetonitrile |
Fluorescence detector |
LOD, 3mg/l |
76 |
|
LC-MS(/MS) |
Serum |
20 antidepressants: amoxapine, amitriptyline, citalopram, clomipramine, dothiepin, doxepin, fluoxetine, imipramine, maprotiline, mianserin, paroxetine, sertraline, trimipramine, nortriptyline, monodesmethylcitalopram, desmethylclomipramine, desipramine, norfluoxetine, desmethylmianserin,N-des methylsertraline |
On-line extraction using column switching |
Cyclone and Xterra MS C18 |
Ammonium acetate in water, formic acid in acetonitrile and water |
Triple stage, ESI, positive mode, SRM |
Analytical range for all compounds, 10-500ng/mL |
150 |
|
LC-MS/MS |
Oral Fluid and Plasma |
amitriptyline, imipramine, clomipramine, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram and venlafaxine and their metabolites nortriptyline, desipramine, norclomipramine and norfluoxetine. |
Automated SPE |
Sunfire C18 IS Column |
Acetonitrile and ammonium formate buffer (pH 3.0; 2 mM) |
tandem mass spectrometer (ESI+ mode) with triple quadrupole |
LLOQ -2 ng/ L (except clomipramine LmsZLOQ -10 ng/ L) for both oral fluid and plasma |
151 |
|
HPLC |
Urine and Plasma |
amitriptyline, imipramine and sertraline |
hollow fiber-based (polypropylene) liquid phase microextraction |
Zorbax Extend C18 column |
0.02 M acetic acid solution and methanol (54:46) (pH 4.0) |
UV-VIS |
LOD found between 0.5 and 0.7 μg L−1 |
85 |
|
GC-MS |
Urine |
fluoxamine, fluoxetine, sertraline, venlafaxine, mitrazapine, citalopram |
SPMES |
CP-SIL C8 |
He- carrier gas (floe rate- 1.2 ml/min) |
MS with Electron Impact Ionisation |
Less than 0.4ng/ml-1 |
Salgado petinal |
Abbreviations:APCI atmospheric pressure chemical ionisation, ESI eletrospray ionisation, LLE liquid-liquid extraction, LOD limitation of detection, LOQ limit of quantification, SIM single ion monitoring, SPE solid-phase extraction, SRM selected reaction monitoring , ESI electron spray ionization, UV ultraviolet, FD fluorescence detector, LC_TMS liquid chromatography tandom mass spectrometry, LC_MS, GC_MS gas chromatography mass spectrometry, RP-HPLC reverse phase high performance liquid chromatography.
Thus, this table is framed for the comparative study of the major analytical approaches used in the detection and identification of Antidepressant Drugs and their metabolites in different biological matrices in order to develop the new methods with the aim to increase the sample throughput and to improve the quality of analytical methods. Thus, analytical methods for the detection of ADs and their metabolites in biological matrices are of interest in the field of forensic toxicology which involves the analysis of drugs and poisons in biological specimens and interpretation of the results to be applied in a court of law. Several analytical methods have been developed for analysis of these antidepressants in biological matrices. These methods provide a good precision and accuracy over the entire analytical range and allowing the development of very rapid and efficient analytical methods by using newer kind of analytical techniques.
Conclusion:
As the subject of Antidepressants toxicity is evolving, newer methods for their analysis are also evolving. However, some classes of Antidepressants drugs are less toxic and well tolerated but can lead to Toxic or Fatal Drug interaction. The research in this field is very active and results in a large number of papers published every year. Therefore they may be encountered in many Clinical and Forensic cases. Therefore, this review is mainly aimed to target latest analytical and instrumental methods used for detection and characterization of Antidepressant drugs and their metabolites in biological test matrices in turn focus on their toxic as well as therapeutic aspects which would be definitely prove to be helpful in future research and still there is lots of work required in this area as it’s prescription rate and toxicity is evolving day by day all over the world and by using non-destructive and sophisticated newer instrumental techniques we can also built a new strategy of examination and investigation for the drugs of interest. However, in this study, a decision about whether a study’s findings are positive or negative cannot always be based strictly on the primary outcome measure. Future trials should also consider, using different kinds of detecting techniques and methods which would allow for easier comparison and interpretation of results across studies as the subject is of global concern and despite the success of such methods there is a continuing need for sustained innovations. Thus, future work in this area will definitely prove to be a promising from both clinical as well as from forensic prospect.
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